Lassa vaccine

Abstract

The present invention relates to recombinant measles viruses expressing Lassa virus polypeptides, in particular immunogenic LASV particles expressed by measles viruses and / or virus-like particles (VLPs) containing Lassa virus proteins. These particles are recombinant infectious particles capable of replicating in a host after administration. The present invention provides means for generating these recombinant infectious particles, in particular nucleic acid constructs, vectors, cells and rescue systems. The present invention also relates to the use of these recombinant infectious particles, in particular in the form of a composition, more specifically in a vaccine formulation, for the treatment or prevention of Lassa virus infection.

Description

FIELD OF THE INVENTION

[0001] The present application generally relates to recombinant gene constructs that comprise a recombinant measles virus and express at least one Lassa virus polypeptide, protein, antigen, or antigenic fragment thereof. The present application also relates to the use of the gene constructs or viruses, and more particularly, to the use of the gene constructs or viruses in inducing protection against Lassa virus (LASV) and / or measles virus (MV or MeV).

[0002] More particularly, the means of the present invention are directed to recombinant nucleic acid constructs that allow the expression of at least one of the following LASV polypeptides, or a truncated form or antigenic fragment thereof: nucleoprotein (NP), glycoprotein precursor (GPC), zinc-binding protein (Z), or a mutant form of the native NP protein (mutant NP or mNP), wherein the exonuclease activity of the NP protein has been reduced.

[0003] The present invention also relates to a recombinant MeV-LASV virus that expresses at least one of the foregoing LASV polypeptides, antigenic fragments, antigens, or truncated forms thereof, namely NP, mNP, GPC, and / or Z. The present invention also relates to immunogenic particles expressed by the measles virus and comprising LASV polypeptides (especially at least the GPC polypeptide or protein, or antigenic fragment thereof), and / or infectious virus-like particles (VLPs) comprising at least the Z polypeptide or protein, or antigenic fragment thereof, said immunogenic particles and / or VLPs being capable of eliciting a cellular response and / or a humoral response against LASV, particularly a T cell response, particularly a CD4+ and / or CD8+ T cell response.

[0004] In particular, the present invention relates to the use of these gene constructs, recombinant nucleic acid constructs, expression vectors such as plasmid vectors, etc., recombinant virus infectious particles (VLPs) in inducing an immunogenic or antigenic response in a host. BACKGROUND OF THE INVENTION

[0005] Lassa virus (LASV) is an old arenavirus of the Arenaviridae family. LASV is an enveloped, single-stranded, two-segmented ambisense RNA virus. Their genome contains two RNA segments, each encoding two proteins, one of each sense, for a total of four viral proteins. The larger segment (about 7 kb) encodes the zinc-binding protein Z. The Z protein regulates replication and transcription. The larger segment also encodes the RNA polymerase L. The smaller segment (about 3.4 kb) encodes the nucleoprotein (NP) and the glycoprotein precursor (GPC), which are cleaved post-translationally into the envelope glycoproteins GP1 and GP2 and the stable signal peptide SSP. These two glycoproteins mediate host cell entry. The L polymerase protein contains the synthetic capacity of the arenavirus. This protein uses the viral RNA template, which consists of genomic RNA encapsulated by the NP protein and the viral ribonucleoprotein. After infection, the virus is delivered to the cytoplasm of the host cell, and the L polymerase protein initiates transcription from the genomic promoter located at the 3' end of each genomic RNA segment. Primary transcription results in the synthesis of mRNAs encoding the viral genes (i.e., the NP and L genes) in the antigenomic direction. Transcription terminates at the distal end of a stem-loop structure within the genomic region. The L polymerase then moves across the genomic region to produce the complementary antigenomic RNA. This RNA serves as a template for the synthesis of the mRNAs for the viral genes GPC and Z and for the synthesis of the full-length genomic RNA.

[0006] LASV is the cause of Lassa fever in humans, a severe hemorrhagic fever. The natural reservoir of the virus is the African rodent Mastomys natalensis. Lassa virus is transmitted from rodents to humans, but the virus can also be transmitted from person to person, causing local outbreaks.

[0007] In the endemic regions of West Africa every year, particularly in Guinea, Liberia, Nigeria, and Sierra Leone, between 100,000 and 300,000 patients, and sometimes up to 500,000 patients, are reported to have Lassa fever. Thus, in these regions, Lassa fever is a major public health problem. The severity of the disease ranges from asymptomatic infection to severe complications that result in fatal hemorrhagic fever. Clinical signs and symptoms include fever, cough, chest pain, difficulty urinating, headache, vomiting, diarrhea, pharyngitis, conjunctivitis, hemorrhage, and facial swelling. The mortality rate of patients infected with LASV is high, and in some areas where LASV is distributed, the mortality rate is approximately 10%. The mortality rate in young children is as high as 50%. In addition, approximately 20% of survivors exhibit long-term complications including hearing impairment. Thus, Lassa fever has a severe impact on the population in these regions and is a major health problem. Recently, the distribution of Lassa fever infections appears to be spreading among other West African countries, as cases have been reported in Mali, Ghana, Côte d'Ivoire, and Burkina Faso over the past decade.

[0008] Although it was discovered in Nigeria in 1969, there is currently no preventive or prophylactic treatment for Lassa fever. Most patients are treated with the antiviral drug ribavirin. Unfortunately, treatment with this drug seems to be most effective only when administered early in the course of the disease and is not completely effective. Treatment should also be completed with supportive care, such as maintaining blood pressure and oxygenation, maintaining fluid and electrolyte balance, and treating any other infections. Thus, it may be difficult to effectively treat patients in the endemic regions of West Africa where Lassa fever is spreading.

[0009] Whether infection results in severe disease or death seems to depend on the host's immune response. Most severe cases involve a defective cellular response in which dendritic cells and macrophages release large amounts of LASV but are not activated and thus do not produce cytokines or produce insufficient cytokines. The severity of the disease, as well as the spread and transmission of the virus within new geographical regions, are serious public health matters that need to be addressed.

[0010] In this context, the development of preventive therapies, such as prophylactic vaccines, is a top priority to meet the needs of these populations. Thus, there is a need for a fully effective treatment that can treat or prevent LASV infection, including preventing the consequences of primary LASV infection, particularly preventing Lassa fever.

[0011] One of the most promising therapies for preventing LASV infection is vaccination, but there is currently no such vaccine. Prevention would be the simplest and safest way to control LASV infection and protect the local population. Despite this urgent need, no candidate vaccine has successfully advanced to clinical trials.

[0012] Accordingly, there is a need for vaccines and products for the preparation of vaccines (such as active ingredients), as well as methods for the production of these products and vaccines. A candidate vaccine should be safe and effective when immunizing a person in need, without significant side effects, and induce the production of antibodies that neutralize LASV, as well as possibly T cells, such as T helper cells and / or cytotoxic T cells. In other words, the vaccine should elicit a strong cellular response and / or humoral response. Advantageously, the vaccine should confer sterilizing immunity after a single immunization. For this purpose, there is a need for a vaccine that can produce LASV proteins and / or LASV VLPs in vivo in infected cells (especially infected cells of the host) and thus provide effective long-lasting immunity, in particular a vaccine that can induce lifelong immunity after only one or two dosing steps.

[0013] Another need is to facilitate vaccination of populations that have difficulty accessing services such as medical centers. A candidate vaccine that can elicit an immune response against two pathogens can enhance the overall health of these populations. Thus, a single vaccination can allow immunization against several pathogens present in the above-mentioned regions. In particular, in order to completely eradicate measles virus (MeV), a vaccine that immunizes against MeV and LASV can clearly protect these populations from these two major threats, especially in West Africa.

[0014] The measles virus was isolated in 1954 (Enders, J.F. and T.C. Peebles. 1954. Propagation in tissue cultures of cytopathogenic agents from patients with measles. Proc. Soc. Exp. Biol. Med. 86:277 - 286). The measles virus is a member of the order Mononegavirales, i.e., a virus with a non - segmented negative - strand RNA genome. The non - segmented genome of MeV has an antimessage polarity, which results in the genomic RNA not being translated either in vivo or in vitro and not being infectious after purification. The transcription and replication of non - segmented (-) - strand RNA viruses and their assembly into virus particles have been studied and reported, especially in Fields virology (3rd edition, volume 1, 1996, Lippincott–Raven publishers–Fields BN et al.). The transcription and replication of the measles virus do not involve the nucleus of the infected cell but occur in the cytoplasm of the host cell, like LASV. The genome of MeV contains genes encoding six major structural proteins (named N, P, M, F, H, and L, respectively), as well as two additional non - structural proteins from the P gene (C and V). The gene order is as follows: from the 3' end of the genomic RNA; N, P (including C and V), M, F, H, and L large polymerase at the 5' end. The genome also contains a non - coding region in the intergenic region M / F. This non - coding region contains approximately 100 nucleotides of untranslated RNA. The genes cited encode the nucleocapsid or nucleoprotein (N), phosphoprotein (P), and large protein (L) of the virus, which together assemble around the genomic RNA to provide the nucleocapsid, hemagglutinin (H), fusion protein (F), and matrix protein (M).

[0015] Attenuated viruses have been derived from the MeV virus to provide vaccine strains, especially the Schwarz strain. The Schwarz measles vaccine is a safe and effective vaccine currently available for the prevention of measles. In addition to providing a vaccine, attenuated measles virus strains (such as the Schwarz strain) have proven to be stable and suitable for use in designing effective delivery vectors for immunization against other viruses, such as Zika virus or Chikungunya virus. In the past 30 years, the measles vaccine has been applied to hundreds of millions of children and has proven its effectiveness and safety. It is produced on a large scale in many countries and sold at low cost. Summary of the Invention

[0016] To at least partially address the drawbacks of the prior art, the inventors have achieved the production of a vaccine active ingredient (or component) based on recombinant gene constructs, in particular recombinant nucleic acid constructs, which contain cloned polynucleotides encoding Lassa virus polypeptides, proteins or antigens or antigenic fragments thereof in an infectious replicating measles virus. The vaccine can be recovered when the recombinant measles virus replicates in a host after administration. Accordingly, the present invention relates to a LASV vaccine, particularly a pediatric vaccine, and to an active ingredient based on an attenuated measles virus strain (such as a commercially available known vaccine strain, particularly the widely used Schwarz measles vaccine). For all these reasons, the inventors have used an attenuated measles virus to generate recombinant measles virus particles that stably express the structural antigens of LASV, particularly its immunogenic particles and / or VLPs. The measles method of the present invention meets all relevant criteria for a future LASV vaccine.

[0017] An object of the present invention is to provide a gene construct, particularly a recombinant gene construct, particularly a nucleic acid construct, for the recovery of an infectious virus from a nucleic acid construct, particularly a measles virus expressing LASV particles and optionally LASV virus-like particles (VLPs).

[0018] Accordingly, the present invention relates to a nucleic acid construct comprising: a cDNA molecule encoding the full-length antigenomic (+) RNA strand of a measles virus and a first heterologous polynucleotide encoding at least one polypeptide or at least one protein or at least one antigen or at least one antigenic fragment thereof of Lassa virus, said at least one polypeptide or at least one protein or at least one antigen or at least one antigenic fragment thereof being selected from the group consisting of: nucleoprotein (NP), mutant nucleoprotein (mNP), zinc-binding protein (Z), and glycoprotein precursor (GPC). The first heterologous polynucleotide is operably cloned into an additional transcription unit (ATU) inserted into the cDNA of the antigenomic (+) RNA strand of MeV. Specific nucleic acid constructs according to this embodiment are illustrated in Figure 1 and Figures 31 to 36 and in the Examples.

[0019] In the above definition, the expression "encoding" includes the ability of cDNA to permit full-length antigenomic (+) RNA transcription, the cDNA being specifically used as a template for transcription and, where appropriate, translated into a product expressed in a cell or cell line. Thus, when the cDNA is a double-stranded molecule, one of the strands has the same nucleotide sequence as the antigenomic (+) RNA of the measles virus (into which the first heterologous polynucleotide is cloned), except that the "U" nucleotide in the cDNA is replaced by a "T" nucleotide. The nucleic acid construct of the invention may comprise regulatory elements controlling the transcription of the coding sequence, in particular a promoter and a termination sequence for transcription, as well as possible enhancers and other cis-acting elements. These regulatory elements may be heterologous with respect to the heterologous polynucleotide produced or derived from a LASV gene and may in particular be regulatory elements of a measles virus strain.

[0020] The expression "operably cloned", which may be replaced by the expression "operably linked", refers to the functional cloning or insertion of a heterologous polynucleotide within the nucleic acid construct of the invention such that the polynucleotide and the nucleic acid construct are specifically and efficiently or highly transcribed and, where appropriate, translated in a cell, cell line, host cell used as part of a rescue system for the production of recombinant infectious MeV particles or MeV expressing at least one polypeptide, or at least one protein, or at least one antigen or at least one antigenic fragment thereof of LASV. In other words, when placed under appropriate conditions, the nucleic acid construct of the invention permits the production of infectious antigenomic (+) RNA which is capable of producing at least one polypeptide, or at least one protein, or at least one antigen, or at least one antigenic fragment thereof of LASV.

[0021] In a particular embodiment of the invention, the nucleic acid construct complies with the six (6) rule of the measles virus genome and comprises a cDNA of the nucleotides encoding the full-length infectious antigenomic (+) RNA strand of MeV but without an operably cloned heterologous polynucleotide. In other words, the cDNA of the nucleotides encoding the full-length infectious antigenomic (+) RNA strand of MeV is a polyhexameric cDNA.

[0022] The organization of the measles virus genome and its replication and transcription processes have been well characterized in the prior art, and the Schwarz vaccine strain of the virus is specifically disclosed in Horikami S.M. and Moyer S.A. (Curr.Top.Microbiol.Immunol.(1995)191,35-50) or Combredet C. et al. (Journal of Virology, November 2003, pages 11546-11554), or the widely recognized negative-sense RNA virus is disclosed in Neumann G. et al. (Journal of General Virology(2002)83,2635-2662).

[0023] The "rule of six" is expressed as the fact that the total number of nucleotides present in the nucleic acid representing the MeV (+)-strand RNA genome or in a nucleic acid construct containing the MeV (+)-strand RNA genome is a multiple of six. The "rule of six" has been recognized in the prior art as a requirement for the total number of nucleotides in the measles virus genome, which enables efficient or optimized replication of MeV genomic RNA. In embodiments of the present invention defining a nucleic acid construct that satisfies the rule of six, the rule applies to a nucleic acid construct specifying a cDNA encoding the full-length MV (+)-strand RNA genome. In this regard, the rule of six applies separately to the cDNA of the nucleotide sequence encoding the full-length infectious anti-genomic (+)-RNA strand of the measles virus, and may or may not apply to a polynucleotide cloned into said cDNA and encoding at least one polypeptide of LASV.

[0024] The nucleic acid constructs of the present invention are in particular purified DNA molecules, which are obtained or obtainable by recombination of at least one polynucleotide of MeV and at least one or several polynucleotides of LASV cloned or ligated operably together.

[0025] According to the present invention, a nucleic acid construct is prepared by cloning one or more polynucleotides into a cDNA encoding the full-length anti-genomic (+)-RNA of the measles virus, the polynucleotide encoding at least one polypeptide or protein or antigen or an antigenic fragment thereof selected from the group consisting of: the GPC protein, NP protein, mNP protein and Z protein of LASV. The MeV genome is shown in Figure 1 A, while several nucleic acid constructs according to the present invention are shown in Figure 1 B and Figures 31 to 36 . Alternatively, synthetic nucleic acid fragments or steps of polymerization from templates, including by PCR, can be used to prepare the nucleic acid constructs of the present invention. The polynucleotides and nucleic acid constructs of the present invention can be prepared according to any known method in the art, and in particular can be cloned, obtained by polymerization especially using the PCR method or can be synthesized.

[0026] A heterologous polynucleotide can be generated by the fusion of several other polynucleotides, each encoding a specific polypeptide of LASV or a specific protein, antigen, or antigenic fragment thereof. For example, a heterologous polynucleotide can be generated by the fusion of polynucleotides, each encoding a single protein, the GPC protein, and the NP protein or the mNP protein. For example, these two polynucleotides are joined in a nucleic acid construct by a linker sequence. Linker sequences are well known in the art and can be short nucleotide sequences containing regulatory sequences of the measles virus or consisting of regulatory sequences of the measles virus.

[0027] Thus, a heterologous polynucleotide can encode a single polypeptide, two different polypeptides, two identical polypeptides, three different polypeptides, two identical polypeptides and another polypeptide, four different polypeptides, two identical polypeptides and two other identical polypeptides, two identical polypeptides and two other different polypeptides, three identical polypeptides and another different polypeptide. Any of these polynucleotides encoding at least two (identical or different) polypeptides can be generated by the fusion of several polynucleotides or can be prepared using synthetic nucleic acid fragments or steps of polymerization from a template, including by PCR. Alternatively, any of these polynucleotides can be cDNA generated after reverse transcription of the genomic RNA of Lassa virus, the cDNA being a complete genomic cDNA or a fragment thereof and encoding a polypeptide of LASV.

[0028] The heterologous polynucleotide, especially the LASV gene, is cloned into an additional transcription unit (ATU) inserted into the cDNA of MeV. ATU sequences are known to those skilled in the art and contain cis-acting sequences necessary for the MeV-dependent expression of the transgene in the MeV cDNA (for the step of cloning into the cDNA of MeV), such as the promoter of the preceding gene, the insert in the multiple cloning site cassette represented by the polynucleotide encoding the LASV polypeptide. The ATU can be further defined as in the disclosure of Billeter et al. in WO97 / 06270. Three ATUs are presented in Figure 1 A. The ATU can also be defined as a multiple cloning cassette inserted within the cDNA of MeV, especially between the N-P intergenic region of the MeV genome and / or between the intergenic H-L region of the MeV genome. The ATU can contain cis-acting sequences necessary for the transcription of the P gene of MeV. The nucleic acid sequences of different ATUs (especially ATU1 and ATU2) can be the same.

[0029] The ATU is usually located between two CTT codons corresponding to the start codon and the stop codon of the polymerase respectively. The ATU may further contain ATG and TAG codons, which respectively correspond to the start codon and the stop codon for translating the heterologous polynucleotide cloned within the ATU. Alternatively, the ATU is located between the ATG and TAG codons, which respectively correspond to the start codon and the stop codon for translating the heterologous polynucleotide cloned within the ATU. The ATU may further contain ATG and TAG codons, which respectively correspond to the start codon and the stop codon for translating the heterologous polynucleotide cloned within the ATU. In a preferred embodiment of the present invention, the ATU is a polynucleotide comprising or consisting of SEQ ID No: 16.

[0030] SEQ ID No: 16

[0031] SEQ ID No: 16 is the ATU sequence located within the cDNA molecule encoding the full-length antigenomic (+) RNA strand of the measles virus. The bold are the CTT codons corresponding to the start codon and the stop codon of the polymerase respectively. The ATG and TAG codons corresponding to the start codon and the stop codon for translating the heterologous polynucleotide cloned within the ATU are underlined.

[0032] CTTAGGAACCAGGTCCACACAGCCGCCAGCCCATCAacgcgtacgATG*TAGgcgcgca gcgcttagacgtctcgcga TCG ATACTAGTACAACCTAAATCCATTATAAAAAACTT

[0033] Wherein, * corresponds to the sequence polynucleotide of the heterologous codon-optimized sequence encoding at least one LASV polypeptide.

[0034] The ATU having a heterologous polynucleotide encoding the GPC polypeptide is located, for example, between amino acid residues 3487 and 5071 of SEQ ID No: 9. SEQ ID No: 17 corresponds to the ATU, which contains the codon-optimized heterologous polynucleotide encoding the GPC protein as a cloning insert.

[0035] The ATU (designated ATU2) is located between the P gene and the M gene of MeV. Another ATU (designated ATU1) is located upstream of the N gene of MeV. Another ATU (designated ATU3) is located between the H and L genes of MeV. It has been observed that transcription of the viral RNA of MeV follows a gradient from the 5'-end to the 3'-end. This explains that if a heterologous polynucleotide is inserted into ATU1, ATU2 or ATU3, depending on the position of insertion of the heterologous polynucleotide, its expression level will vary and be more or less efficient.

[0036] The term "polypeptide" is used interchangeably with the terms "antigen" or "protein" or "antigenic fragment" and defines a molecule formed by the linkage of amino acid residues. In particular, the polypeptides disclosed in the present application are derived from LASV and are antigens, proteins, structural proteins or antigenic fragments thereof, which may be identical to the native protein or may be derived by mutation, including by substitution (especially substitution of conservative amino acid residues) or addition of amino acid residues or by post-translational secondary modification or by deletion of a portion of the native protein such that the fragment has a reduced size relative to the native reference protein. Fragments are included in the present invention to the extent that they carry epitopes of the native protein suitable for eliciting an immune response in a host, particularly a human host (including a pediatric host), preferably an immune response capable of protecting against LASV infection or LASV-related diseases. The epitopes are particularly of the type of T epitopes involved in eliciting a cell-mediated immune response (CMI response). T epitopes participate in the stimulation of T cells by presenting certain portions of the T cell epitopes that can bind to class II MHC molecules, resulting in the activation of T cells. Alternatively, the epitope may be of the B type involved in activating the production of antibodies in a host that has been administered the protein or in which the protein is expressed after administration of the infectious replication particles of the present invention. The size of the fragment may represent more than 50%, preferably at least 90% or 95% of the amino acid sequence size of the native protein of the LASV strain Josiah. The polypeptide may have at least 50% (preferably at least 60%, preferably at least 70%, preferably at least 85% or at least 95%) identity with the native protein of the LASV strain Josiah.

[0037] In a particular embodiment of the invention, each polynucleotide operably cloned into the cDNA of the antigenomic (+) RNA encodes a polypeptide comprising an epitope located within any one of the LASV polypeptides. According to this embodiment, the epitope sequence has 100% identity with the epitope sequence of the native LASV protein. Such epitopes are available in the Immune Epitope Database and Analysis Resource ( www.iedb.org) are listed. Within the polypeptides of LASV encoded by polynucleotides and having an epitope sequence as defined herein, the amino acid residues that do not belong to any epitope may differ from the sequence of the native LASV protein. "Polypeptides of LASV" means "polypeptides" (polypeptides, antigens, proteins or antigenic fragments thereof) as defined herein, the amino acid sequence of which is identical to the counterpart in a LASV strain (especially LASV strain Josiah), including polypeptides that are the natural mature or precursor of a LASV protein, or an antigenic fragment or mutant as defined herein, in particular an antigenic fragment or mutant having at least 50%, at least 80%, particularly advantageously at least 90% or preferably at least 95% amino acid sequence identity with a naturally occurring LASV GPC, NP or Z protein. Amino acid sequence identity can be determined by alignment by a person skilled in the art using manual alignment or using a variety of available alignment programs (e.g., BLASTP - http: / / blast.ncbi.nlm.nih.gov / ). Fragments or mutants of the LASV polypeptides of the present invention can be defined relative to the specific amino acid sequences shown herein, especially amino acid sequences selected from SEQ ID No: 1, SEQ ID No: 3, SEQ ID No: 5 and SEQ ID No: 7. In a particular embodiment of the present invention, the polypeptides have at least 50%, at least 80%, particularly advantageously at least 90% or preferably at least 95% amino acid sequence identity with their native proteins of LASV strain Josiah or with the polypeptides of SEQ ID No: 1, SEQ ID No: 3, SEQ ID No: 5 or SEQ ID No: 7.

[0038] According to one aspect of the invention, polynucleotides encoding at least one polypeptide of LASV are generated or derived from the genome of a separated and purified LASV wild strain (including any Lassa strain whose genome has been fully or partially sequenced). At least some of these sequences can be found in the NCBI nucleotide database. In particular, the polynucleotides encoding at least one LASV polypeptide can be derived or generated from any Lassa strain sequenced and cited in Clinical Sequencing Uncovers Origins and Evolution of Lassa Virus (Andersen Kristian G et al.; 2015; Cell. August 13, 2015; 162(4):738–750. doi:10.1016 / j.cell.2015.07.020) (specifically in the supplementary data of the publication listing the strain names and sequence accession references). Preferably, the polynucleotide is generated or derived from the Josiah strain, and the genomic sequences of the two RNA segments of this strain can be found under GenBank accession number J04324.1 (short genomic RNA encoding the NP protein and GPC protein) and European Nucleotide Archive accession number U73034.2 (long genomic RNA encoding the Z protein and L protein). The native proteins of the LASV strain Josiah can be defined as having sequences produced by RNA segments found under GenBank accession number J04324.1 (short genomic RNA encoding the NP protein and GPC protein) and European Nucleotide Archive accession number U73034.2 (long genomic RNA). The term "derived" as it appears in the definition of the polynucleotide only means that the sequence of the polynucleotide can be the same as the corresponding sequence in the LASV strain or can vary to the extent of encoding a polypeptide, antigen, protein, or fragment thereof of LASV that meets the definition of "polypeptide" of the present invention. In particular, when codon-optimized for such sequences, the polynucleotide is derived from the nucleic acid of the LASV strain. Thus, the term does not limit the manner of production of the polynucleotide.

[0039] Alternatively, the fragment can be a short polypeptide having at least 10 amino acid residues and having an epitope of the native protein listed in the Immune Epitope Database and Analysis Resource (www.iedb.org). In this regard, the fragment also includes multi-epitopes.

[0040] According to another embodiment of the invention, the nucleic acid construct further comprises a second heterologous polynucleotide encoding at least one polypeptide of LASV or an antigenic fragment thereof, said at least one polypeptide or antigenic fragment thereof being selected from the group consisting of: GPC protein, NP protein, mNP protein and Z protein, the second heterologous polynucleotide being operably cloned into another ATU at a position different from that of the first cloned heterologous polynucleotide (preferably upstream of the N gene of MeV), said another ATU (especially ATU1) being inserted upstream of the N gene of MeV. The second heterologous polynucleotide or an antigenic fragment thereof particularly encodes at least one polypeptide or an antigenic fragment thereof different from the polypeptide encoded by the first heterologous polynucleotide.

[0041] According to this embodiment, advantageously, another ATU (designated ATU1) is located in the N-terminal sequence of the cDNA molecule encoding the full-length (+) RNA strand of the MeV antigenome upstream of the N gene of MeV, while another ATU (ATU2) is preferably located between the P gene and the M gene of the virus. Since the transcription of the viral RNA of MeV follows a gradient from the 5'-end to the 3'-end, the inventors have found that when the Z protein is encoded by at least one heterologous polynucleotide, cloning two polynucleotides at different positions in the cDNA encoding the full-length antigenome (+) RNA of measles virus may result in a higher yield of antigenic particles and / or LASV virus-like particles (VLPs), while this yield may be less significant when the polynucleotides are both cloned at the same position. In addition, cloning the heterologous polynucleotides at different positions can reduce the attenuation of the expression of the encoded polypeptides. Indeed, when several genes are cloned within a single ATU, it may result in a decrease in the expression of the encoded polypeptides. The specific nucleic acid construct according to this embodiment is shown in Figure 1 b and in the examples.

[0042] In another ATU, the second polynucleotide may encode any one of the polypeptides of LASV or an antigenic fragment thereof listed above. Thus, the second polynucleotide located within another ATU may encode the same polypeptide as the first polynucleotide inserted within the first ATU, or the second polynucleotide may share at least one polypeptide encoded by the first polynucleotide. In a preferred embodiment of the invention, the first polynucleotide and the second polynucleotide encode at least one different polypeptide or an antigenic fragment thereof.

[0043] A cDNA molecule encoding the full-length antigenomic (+) RNA strand of MeV can be specific to an attenuated strain of MeV or can be obtained from an attenuated strain of MeV. An "attenuated strain" of MeV is defined as a strain that is non-toxic or less virulent than the parental strain in the same host, while maintaining immunogenicity and potential adjuvanticity when administered in a host to preserve immunodominant T-cell and B-cell epitopes and possibly an adjuvant (such as an inducible T-cell costimulatory protein or cytokine IL-12).

[0044] Accordingly, an attenuated strain of measles virus is a strain that has been serially passaged on selected cells and possibly adapted to other cells to produce a seed strain suitable for the preparation of a human vaccine strain, which has a stable genome and does not permit reversion to pathogenicity or integration into the host chromosome. As a specific "attenuated strain", the approved strain of the vaccine is an attenuated strain suitable for the present invention that meets the criteria defined by the FDA (U.S. Food and Drug Administration); that is, after rigorous review of laboratory and clinical data (www.fda.gov / cber / vaccine / vacappr.htm), it meets the standards of safety, efficacy, quality, and reproducibility.

[0045] In particular, a cDNA molecule encoding the full-length antigenomic (+) RNA strand of MeV is obtained from an attenuated virus strain selected from the group consisting of Schwarz strain, Zagreb strain, AIK-C strain, Moraten strain, Philips strain, Beckenham 4A strain, Beckenham 16 strain, Edmonston seed A strain, Edmonston seed B strain, CAM-70 strain, TD 97 strain, Leningrad-16 strain, Shanghai 191 strain, and Belgrade strain. All of these strains have been described in the prior art. The present invention particularly uses strains that have been permitted to be used as commercial vaccines. In particular, a cDNA molecule encoding the full-length antigenomic (+) RNA strand of MeV is obtained from the Schwarz strain.

[0046] According to a specific embodiment of the present invention, the cDNA molecule is placed under the control of a heterologous expression control sequence.

[0047] Inserting such a control for cDNA expression is advantageous when seeking expression of the cDNA in cell types that cannot utilize their native control sequences to fully transcribe the cDNA.

[0048] According to a specific embodiment of the present invention, the heterologous expression control sequence comprises a T7 promoter and a T7 terminator sequence. These sequences are located at the 5' and 3' ends of the coding sequence of the full-length antigenomic (+) RNA strand of MeV, respectively, and are derived from the adjacent sequences surrounding the coding sequence.

[0049] In a specific embodiment of the present invention, the cDNA molecule defined above is modified, i.e., it contains additional nucleotide sequences or motifs.

[0050] In a preferred embodiment, the cDNA molecule used according to the present invention further contains a GGG motif at its 5' end (adjacent to the first nucleotide of the nucleotide sequence encoding the full-length antigenome (+) RNA strand of the MeV approved vaccine strain), followed by a hammerhead ribozyme sequence, and contains a ribozyme sequence at its 3' end (adjacent to the last nucleotide of the said nucleotide sequence encoding the full-length antigenome (+) RNA strand). The hepatitis delta virus ribozyme (δ) is suitable for carrying out this preferred embodiment.

[0051] The GGG motif located at the 5′ end adjacent to the first nucleotide of the above-mentioned coding sequence improves the transcription efficiency of the cDNA coding sequence. The requirement for the correct assembly of measles virus particles is that the cDNA encoding the antigenome (+) RNA conforms to the rule of six. When the GGG motif is added, a ribozyme is also added to the 5' end of the cDNA coding sequence, i.e., the 3' end of the GGG motif, so as to be able to cleave the transcript at the first coding nucleotide of the full-length antigenome (+) RNA strand of MeV.

[0052] To prepare the nucleic acid construct of the present invention, a cDNA molecule encoding the full-length antigenome (+) RNA of the measles virus disclosed in the prior art was prepared by known methods. When the obtained cDNA is inserted into a vector such as a plasmid, the obtained cDNA provides a basis in particular for a genomic vector involved in the rescue of recombinant measles virus particles.

[0053] The specific cDNA molecules suitable for preparing the nucleic acid constructs of the present invention were obtained using the Schwarz strain of measles virus. Plasmid pTM-MVSchw contains infectious MeV cDNA corresponding to the antigenome of the Schwarz MV vaccine strain and was used to prepare recombinant vectors containing the heterologous polynucleotides of the present invention. This plasmid pTM-MVSchw has been described elsewhere (Combredet, C. et al., A molecularly cloned Schwarz strain of measles virus vaccine induces strong immune responses in macaques and transgenic mice. J Virol, 2003. 77(21): pp. 11546-54). Thus, the cDNA used in the present invention can be obtained as disclosed in WO2004 / 000876, or can be obtained from plasmid pTM-MVSchw deposited at the CNCM under the number I-2889 by the Institut Pasteur on June 12, 2002, the sequence of which is disclosed in WO2004 / 000876 and incorporated herein by reference. Plasmid pTM-MVSchw was obtained from the Bluescript plasmid and contains a polynucleotide encoding the full-length measles virus (+) RNA strand of the Schwarz strain under the control of the promoter of T7 RNA polymerase. It has 18,967 nucleotides and the sequence represented by SEQ ID NO: 15. cDNA molecules of other MeV strains (also referred to as cDNA of measles virus or MeV cDNA for convenience) can be obtained similarly from nucleic acids purified from virus particles of attenuated MeV (such as those described herein). Another transcription unit can be a multiple cloning site cassette previously inserted into the vector, as described by Combredet et al. (2003). The ATU can contain cis-acting sequences necessary for the transcription of the inserted LASV gene. The heterologous polynucleotide is cloned or inserted into the additional transcription unit (ATU) defined above.

[0054] The heterologous polynucleotide can also be cloned or inserted into another ATU. For example, a third ATU can be inserted between the H gene and the L gene of MeV, and the first heterologous polynucleotide or the second heterologous polynucleotide can be cloned or inserted into this third ATU. In a specific embodiment of the present invention, the nucleic acid construct can comprise: a first heterologous polynucleotide inserted into a first ATU, a second heterologous polynucleotide sequence inserted into a second ATU at a position different from the first ATU, and a third heterologous polynucleotide sequence inserted into a third ATU at a position different from the first ATU and the second ATU.

[0055] In a preferred embodiment, the nucleic acid construct comprises a heterologous polynucleotide encoding a specifically mutated NP protein or an antigenic fragment thereof. The native NP protein can be mutated to reduce the exonuclease activity of the NP protein. The exonuclease activity-reduced NP protein can be assayed by a luciferase assay using a luciferase reporter gene placed under the control of an IRF3-dependent promoter (as described in PMID: 21085117 and as Figure 29 shown). NP is involved in virus-induced inhibition of type I IFN signaling (Martinez-Sobrido, 2006). This activity is associated with the C-terminal domain of the native NP protein. Functional analysis has confirmed the exonuclease activity of LASV NP, which has been shown to be a key step in its type I IFN counteracting function (Qi, 2010). Therefore, the inventors introduced two mutations within the exonuclease domain of the NP protein. The exonuclease domain of the NP protein is located within the C-terminal domain of the NP protein, particularly between amino acid residues 341 and 569 of SEQ ID No: 3. Thus, the mutated NP protein is particularly produced from the native NP protein mutated within the exonuclease domain as defined above (by deleting and / or adding and / or substituting any amino acid residue), and its exonuclease activity is reduced according to the luciferase assay described above. In particular, substituting at least one of the amino acid residues D389, E391, D466, D533, and H528 of SEQ ID No: 3 can result in a mutated NP protein without exonuclease activity. In particular, the amino acid residue at position 389 of SEQ ID No: 3 can be mutated, for example, by substituting aspartic acid with alanine. Alternatively, the amino acid residue at position 392 of SEQ ID No: 3 can be mutated, for example, by substituting glycine with alanine. In a preferred embodiment, the two amino acid residues at positions 389 and 392 of SEQ ID No: 3 are mutated by substitution. In a more preferred embodiment, the mNP protein has the sequence of SEQ ID No: 5.

[0056] According to this embodiment, the mNP polypeptide encoded by the polynucleotide allows for the induction of type I IFN. In other words, the immunosuppressive function of native NP is switched off in mNP. Thus, a nucleic acid construct is provided that comprises a polynucleotide that enhances the efficiency of the immunogenicity of chimeric recombinant MeV-LASV infectious particles.

[0057] According to a preferred embodiment, the invention also relates to the modification, particularly optimization, of the polynucleotide to allow for the efficient expression of LASV polypeptides, proteins, antigens, or fragments thereof in a host cell.

[0058] Thus, optimization of the polynucleotide sequence can be carried out to avoid cis - acting domains of nucleic acid molecules: internal TATA boxes, Chi - sites and ribosome entry sites; AT - rich or GC - rich sequence stretches; ARE, INS, CRS sequence elements; repetitive sequences and RNA secondary structures; cryptic splice donor and acceptor sites, branch points.

[0059] The optimized polynucleotide can also be codon - optimized for expression in a particular cell type, in particular, it can be modified for Maccaca codon usage or human codon usage. This optimization allows increasing the efficiency of production of chimeric infectious particles in cells without affecting the amino acid composition of the expressed protein.

[0060] In particular, polynucleotides encoding LASV polypeptides can be optimized by modifying the wobble position in the codons without affecting the identity of the amino acid residue translated from the codon relative to the original codon.

[0061] Optimization has also been carried out to avoid editing - like sequences of measles virus. Editing of measles virus transcripts is a process that occurs particularly in transcripts encoded by the P gene of measles virus. This editing, which is carried out by inserting additional G residues at specific sites in the P transcript, results in a new protein that is truncated compared to the P protein. Expression of the V protein, which contains a unique carboxyl terminus, can be caused by the addition of only a single G residue (Cattaneo R et al., Cell. March 10, 1989; 56(5):759 - 64).

[0062] In the polynucleotides according to this particular embodiment of the invention, the following editing - like sequences from measles virus can be mutated: AAAGGG, AAAAAG, GGGAAA, GGGAAA, GGGAAA, GGGAAA, and their complementary sequences: TTTCCC, TTTTCC, CCCTTT, CCCCTT. For example, AAAGGG can be mutated to AAAGGC, AAAAAG can be mutated to AGAAGG or TAAAGG or GAAAGG, and GGGAAA can be mutated to GCGAAA.

[0063] Thus, the heterologous polynucleotide can comprise any one of the following sequences, or more than one of the following sequences, or at least two of the following sequences, or at least three of the following sequences, or all four of the following sequences:

[0064] - SEQ ID No: 2 encoding the GPC protein; and / or

[0065] - SEQ ID No: 4 encoding the NP protein; and / or

[0066] - SEQ ID No: 6 encoding the mNP protein; and / or

[0067] - SEQ ID No: 8 encoding the Z protein.

[0068] In a heterologous polynucleotide, each of the sequences defined above may occur once or more than once. In a preferred embodiment of the invention, each sequence occurs once within a single heterologous polynucleotide, or each sequence occurs once within the combined heterologous polynucleotides.

[0069] According to any of the specific embodiments of the present invention, there is provided a nucleic acid construct comprising a polynucleotide that increases the efficiency of production of chimeric recombinant MeV-LASV infectious particles.

[0070] Alternatively or complementarily, the heterologous polynucleotide may encode any one of the following polypeptides or antigenic fragments thereof, or at least two of the following polypeptides, or at least three of the following polypeptides, or all four of the following polypeptides:

[0071] - the GPC protein of SEQ ID No: 1 or an antigenic fragment thereof; and / or

[0072] - the NP protein of SEQ ID No: 3 or an antigenic fragment thereof; and / or

[0073] - the mNP protein of SEQ ID No: 5 or an antigenic fragment thereof; and / or

[0074] - the Z protein of SEQ ID No: 7 or an antigenic fragment thereof.

[0075] It should be noted that the polynucleotide may encode the polypeptides defined above once or more than once. In a preferred embodiment, each polypeptide is encoded once within a single heterologous polynucleotide, and more preferably, each polypeptide is encoded once within multiple polypeptides. According to a specific embodiment of the present invention, several polynucleotides in which each polynucleotide encodes at least one LASV protein are combined or fused to form a polynucleotide encoding several proteins of LASV. These polynucleotides may be distinguished from each other in that they encode proteins of various strains of LASV, or they encode different proteins of a LASV strain.

[0076] In a specific embodiment, the nucleic acid construct of the present invention comprises the following polynucleotides from the 5' to the 3' end:

[0077] (a) a polynucleotide encoding the N protein of MeV;

[0078] (b) a polynucleotide encoding the P protein of MeV;

[0079] (c) A first heterologous polynucleotide encoding at least one polypeptide selected from the GPC protein, NP protein, mNP protein, and Z protein of LASV, or an antigenic fragment thereof; in particular, encoding a single polypeptide, which is the GPC protein or an antigenic fragment thereof; or encoding at least two polypeptides, which are the GPC protein or an antigenic fragment thereof and the NP protein or mNP protein, or an antigenic fragment thereof; in particular, encoding the GPC protein and mNP protein, wherein the first polynucleotide is particularly operably cloned in an ATU, particularly ATU2;

[0080] (d) A polynucleotide encoding the M protein of MeV;

[0081] (e) A polynucleotide encoding the F protein of MeV;

[0082] (f) A polynucleotide encoding the H protein of MeV;

[0083] (g) A polynucleotide encoding the L protein of MeV;

[0084] Wherein, under the control of viral replication and transcription regulators such as the MeV leader sequence and trailing sequence, the polynucleotides are operably linked in a nucleic acid construct.

[0085] Figure 1 Several examples of this embodiment obtained according to the present invention are schematically shown in B: constructs named MeV-GPC LASV ; MeV-NP+GPC LASV ; MeV-NP ExoN +GPC LASV belong to this specific embodiment, but also include Figure 1 other constructs not shown in B, such as MeV-GPC LASV +NP; MeV-GPC LASV +NP ExoN ; MeV-Z+GPC LASV ; MeV-GPC LASV +Z; MeV-Z+NP; MeV-Z+NP ExoN ; MeV-NP+Z; MeV-NP ExoN +Z; MeV-Z+GPC LASV +NP; MeV-Z+GPC LASV +NP ExoN ; MeV-Z-NP-GPC LASV ; MeV-Z-NP ExoN -GPC LASV ; MeV-GPC LASV +NP+Z; MeV-GPC LASV +NP ExoN+Z; MeV - GPC LASV +Z + NP; MeV - GPC LASV +Z + NP ExoN ; MeV - NP + GPC LASV +Z; MeV - NP - Z + GPC LASV ; MeV - NP ExoN +GPC LASV +Z; MeV - NP ExoN- Z + GPC LASV ;

[0086] Wherein,

[0087] MeV corresponds to a cDNA molecule encoding the full - length antigenomic (+) RNA strand of measles virus (MeV);

[0088] GPC LASV corresponds to a polynucleotide encoding a polypeptide or an antigenic fragment thereof that encodes the GPC protein;

[0089] NP corresponds to a polynucleotide encoding a polypeptide or an antigenic fragment thereof that encodes the NP protein.

[0090] NP ExoN corresponds to a polynucleotide encoding a polypeptide or an antigenic fragment thereof that encodes the mNP protein;

[0091] Z corresponds to a polynucleotide encoding a polypeptide or an antigenic fragment thereof that encodes the Z protein;

[0092] The expressions "N protein", "P protein", "M protein", "F protein", "H protein" and "L protein" respectively refer to the nucleoprotein (N), phosphoprotein (P), matrix protein (M), fusion protein (F), hemagglutinin protein (H) and large RNA polymerase protein (L) of measles virus, and encompass their respective polypeptides or antigenic fragments. These components have been determined in the prior art and are particularly disclosed in Fields, Virology (Knipe & Howley, 2001).

[0093] In another specific embodiment of the present invention, the nucleic acid construct comprises the following polynucleotides from the 5' to the 3' end:

[0094] (a) A second heterologous polynucleotide encoding at least one polypeptide or an antigenic fragment thereof selected from the GPC protein, NP protein, mNP protein and Z protein of LASV; particularly encoding the Z protein or an antigenic fragment thereof, wherein the second polynucleotide is operably cloned in an ATU located upstream of the N gene of MeV, particularly in ATU1;

[0095] (b) A polynucleotide encoding the N protein of MeV;

[0096] (c) A polynucleotide encoding the P protein of MeV;

[0097] (d) A first heterologous polynucleotide encoding at least one polypeptide selected from the GPC protein, NP protein, mNP protein, and Z protein of LASV or an antigenic fragment thereof; in particular, encoding a single polypeptide, which is the GPC protein or an antigenic fragment thereof; or encoding at least two polypeptides, which are the GPC protein or an antigenic fragment thereof and the NP protein or mNP protein, or an antigenic fragment thereof; in particular, encoding the GPC protein and the mNP protein, wherein the first polynucleotide is particularly operably cloned in an ATU, particularly ATU2;

[0098] (e) A polynucleotide encoding the M protein of MeV;

[0099] (f) A polynucleotide encoding the F protein of MeV;

[0100] (g) A polynucleotide encoding the H protein of MeV;

[0101] (h) A polynucleotide encoding the L protein of MeV,

[0102] wherein the polynucleotide is operably linked in a nucleic acid construct under the control of viral replication and transcription regulators such as the MeV leader sequence and trailer sequence.

[0103] Figure 1 Several examples of this embodiment are schematically shown in B: constructs named Z-MeV-GPC LASV ; Z-MeV-NP+GPC LASV ; Z-MeV-NP ExoN +GPC LASV are included in this particular embodiment. When the LASV protein is named after MeV, the protein is cloned into another transcription unit located upstream of the N gene of MeV. It should be noted that several constructs not shown are also included in this embodiment. For example, the heterologous polynucleotide can be cloned into a third ATU. Corresponding to Z-MeV-GPC LASV (ATU2)+NP(ATU3) or Z-MeV-NP(ATU2)-GPC LASV (ATU3) or Z-MeV-GPC LASV (ATU2)+mNP(ATU3) or Z-MeV-mNP(ATU2)-GPC LASVNucleic acid constructs of (ATU3) are also included in the present invention. It should be noted that heterologous polynucleotides encoding at least one or any one of the Z polypeptide, GPC polypeptide, and / or NP or mNP polypeptide can be inserted into ATU3. The various terms used herein have the same meanings as those used in the previous specific embodiments.

[0104] In a specific embodiment of the present invention, the nucleic acid construct contains, within a first heterologous polynucleotide, a nucleic acid encoding an NP protein (preferably the NP protein of SEQ ID No: 3) or an antigenic fragment thereof; and a nucleic acid encoding a GPC protein (preferably the GPC protein of SEQ ID No: 1). In a preferred embodiment, the first heterologous polynucleotide is cloned between the P gene and the M gene of MeV, preferably in ATU2 as defined above.

[0105] In a specific embodiment of the present invention, the nucleic acid construct contains, within a first heterologous polynucleotide, the nucleic acid of SEQ ID No: 4 encoding an NP protein and the nucleic acid of SEQ ID No: 2 encoding a GPC protein, preferably the two nucleic acids are separated by a linker sequence. In a preferred embodiment, the nucleic acid of SEQ ID No: 4 is upstream of the nucleic acid of SEQ ID No: 2. For example, this is illustrated Figure 1 in B with a construct named MeV-NP+GPC LASV as follows.

[0106] In a specific embodiment of the present invention, the nucleic acid construct contains, within a first heterologous polynucleotide, a nucleic acid encoding an mNP protein (preferably the mNP protein of SEQ ID No: 5) or an antigenic fragment thereof; and a nucleic acid encoding a GPC protein (preferably the GPC protein of SEQ ID No: 1).

[0107] In a specific embodiment of the present invention, the nucleic acid construct contains, within a first heterologous polynucleotide, the nucleic acid of SEQ ID No: 6 encoding an mNP protein and the nucleic acid of SEQ ID No: 2 encoding a GPC protein, preferably the two nucleic acids are separated by a linker sequence. In a preferred embodiment, the nucleic acid of SEQ ID No: 6 is upstream (towards the 5' end of the construct) of the nucleic acid of SEQ ID No: 2, as Figure 1 shown in B, where the construct is named MeV-NP ExoN +GPC LASV . In a preferred embodiment, the first heterologous polynucleotide is cloned between the P gene and the M gene of MeV, preferably in ATU2 as defined above.

[0108] In a specific embodiment of the present invention, the nucleic acid construct comprises a first heterologous polynucleotide and a second heterologous polynucleotide, wherein:

[0109] - The second heterologous polynucleotide comprises a nucleic acid encoding a Z protein or an antigenic fragment thereof, preferably the Z protein of SEQ ID No: 7; preferably the second heterologous polynucleotide is cloned in ATU1 as defined above,

[0110] - The first heterologous polynucleotide comprises a nucleic acid encoding a GPC protein or an antigenic fragment thereof, preferably the GPC protein of SEQ ID No: 1, and preferably the first heterologous polynucleotide is cloned in ATU2 as defined above.

[0111] In a specific embodiment of the present invention, the nucleic acid construct comprises a first heterologous polynucleotide and a second heterologous polynucleotide, wherein:

[0112] - The second heterologous polynucleotide comprises the nucleic acid of SEQ ID No: 8 encoding the Z protein, and preferably the second heterologous polynucleotide is cloned in ATU1 as defined above,

[0113] - The first heterologous polynucleotide comprises the nucleic acid of SEQ ID No: 2 encoding the GPC protein, and preferably the first heterologous polynucleotide is cloned in ATU2 as defined above.

[0114] In a specific embodiment of the present invention, the nucleic acid construct comprises a recombinant cDNA, the sequence of which is selected from the following:

[0115] SEQ ID No: 9 (MeV-GPC);

[0116] SEQ ID No: 10 (MeV-NP-GPC);

[0117] SEQ ID No: 11 (MeV-mNP-GPC);

[0118] SED ID No: 12 (Z-MeV-GPC);

[0119] SEQ ID No: 13 (Z-MeV-NP-GPC); and

[0120] SEQ ID No: 14 (Z-MeV-mNP-GPC),

[0121] wherein the sequences are described as follows:

[0122] SEQ ID NO: 9

[0123] SEQ ID No: 9 is the sequence of a nucleic acid construct according to a specific embodiment of the present invention, wherein the construct comprises the pTM1-MVSchwarz vector, and the sequence encoding the GPC protein of the LASV strain Josiah has been cloned in additional transcription unit 2.

[0124] SEQ ID NO: 10

[0125] SEQ ID No: 10 is the sequence of a nucleic acid construct according to another specific embodiment of the present invention, wherein the construct comprises the pTM1-MVSchwarz vector, and the sequence encoding the GPC protein of the LASV strain Josiah has been cloned in additional transcription unit 2, and the sequence encoding the NP protein of the LASV strain Josiah has been cloned in additional transcription unit 2.

[0126] SEQ ID NO: 11

[0127] SEQ ID No: 11 is the sequence of a nucleic acid construct according to another specific embodiment of the present invention, wherein the construct comprises the pTM1-MVSchwarz vector, and the sequence encoding the GPC protein of the LASV strain Josiah has been cloned in additional transcription unit 2, and the sequence encoding the mutant NP protein of the LASV strain Josiah has been cloned in additional transcription unit 2.

[0128] SEQ ID NO: 12

[0129] SEQ ID No: 12 is the sequence of a nucleic acid construct according to another specific embodiment of the present invention, wherein the construct comprises the pTM1-MVSchwarz vector, and the sequence encoding the GPC protein of the LASV strain Josiah has been cloned in additional transcription unit 2, and the sequence encoding the Z protein of the LASV strain Josiah has been cloned in additional transcription unit 1.

[0130] SEQ ID NO: 13

[0131] SEQ ID No: 13 is the sequence of a nucleic acid construct according to another specific embodiment of the present invention, wherein the construct comprises the pTM1-MVSchwarz vector, and the sequence encoding the GPC protein of the LASV strain Josiah has been cloned in additional transcription unit 2, and the sequence encoding the NP protein of the LASV strain Josiah has been cloned in additional transcription unit 2, and the sequence encoding the Z protein of the LASV strain Josiah has been cloned in additional transcription unit 1.

[0132] SEQ ID NO: 14

[0133] SEQ ID No: 14 is the sequence of a nucleic acid construct according to another specific embodiment of the present invention, wherein said construct comprises the pTM1-MVSchwarz vector, wherein the sequence encoding the GPC protein of the LASV strain Josiah has been cloned in additional transcription unit 2, the sequence encoding the mutant NP protein of the LASV strain Josiah has been cloned in additional transcription unit 2, and the sequence encoding the Z protein of the LASV strain Josiah has been cloned in additional transcription unit 1.

[0134] The present invention also relates to transfer vectors which can be used to prepare recombinant MeV-LASV particles when rescued from helper cells or producer cells. Figures 31 to 36 Several transfer vectors are shown in

[0135] In a preferred embodiment of the present invention, the transfer vector is a transfer vector plasmid suitable for transfection of helper cells or producer cells and comprises a nucleic acid construct according to the present invention. The transfer vector plasmid can be obtained from the Bluescript plasmid and can be obtained by cloning the heterologous polynucleotide of the present invention in the pTM-MVSchw plasmid described above. In a specific embodiment of the present invention, the transfer plasmid vector has the sequence of SEQ ID No: 9, SEQ ID No: 10, SEQ ID No: 11, SEQ ID No: 12, SEQ ID No: 13 or SEQ ID No: 14.

[0136] The nucleic acid constructs and transfer plasmid vectors of the present invention are suitable and used for the preparation of recombinant infectious replicative recombinant measles-Lassa virus (MeV-LASV). Therefore, the nucleic acid constructs and transfer plasmid vectors are intended to be inserted into a transfer genomic vector, which thus contains a cDNA molecule of measles virus, especially the Schwarz strain, for the production of the recombinant MeV-LASV virus and the expression of LASV polypeptides, which may be LASV VLPs when the Z protein is encoded by at least one heterologous polynucleotide. The pTM-MVSchw plasmid is suitable for preparing a transfer vector by inserting the heterologous polynucleotides described herein, which are necessary for the expression of LASV polypeptides, proteins, antigens or antigenic fragments thereof. As used herein, the term "virus-like particle" (VLP) refers to a structure that is similar to a virus in at least one property but has not been proven to be infectious. The virus-like particles according to the present invention do not carry the genetic information encoding the proteins of the virus-like particles. Generally, the virus-like particles lack a viral genome and are thus non-infectious and non-replicative. According to the present invention, virus-like particles can be produced in large quantities and expressed together with the MeV-LASV recombinant particles.

[0137] The present invention also relates to cells or cell lines so transformed by the transfer vector of the present invention and other polynucleotides that provide helper functions and proteins. Therefore, in the cells, there are polynucleotides that encode proteins (preferably proteins that are stably expressed at least for the N protein and P protein that play a role in the transcription and replication of the recombinant virus MeV-LASV particles), especially including the N protein, P protein and L protein of measles virus (i.e., the native MeV proteins or their functional variants capable of forming a ribonucleoprotein (RNP) complex). The N protein and P protein can be expressed in the cells by a plasmid containing their coding sequences, or by a DNA molecule inserted into the cell genome. The L protein can be expressed by a different plasmid. It may be transiently expressed. The helper cells are also capable of expressing an RNA polymerase (possibly a stably expressed RNA polymerase) suitable for ensuring the synthesis of recombinant RNA derived from the nucleic acid constructs of the present invention. The RNA polymerase can be T7 phage polymerase or its nuclear form (nlsT7).

[0138] In one embodiment, the cDNA clone of measles virus is from the same measles virus strain as the N protein and / or P protein and / or L protein. In another embodiment, the cDNA clone of measles virus is from a different virus strain than the N protein and / or P protein and / or L protein.

[0139] When the Z protein is encoded by at least one heterologous polynucleotide, cells transformed or transfected with the nucleic acid construct according to the present invention are capable of producing recombinant measles virus and / or LASV VLPs. Thus, the recombinant measles virus contains the nucleic acid construct of the present invention in its genome and is capable of expressing at least one polypeptide, protein or antigenic fragment of LASV. Therefore, the measles virus of the present invention is capable of expressing the GPC protein or GPC polypeptide or its antigenic fragment; and / or the NP protein or NP polypeptide or its antigenic fragment; and / or the mNP protein, or mNP polypeptide, or its antigenic fragment; and / or the Z protein, or Z polypeptide, or its antigenic fragment. The LASV VLP contains at least the Z protein or its antigenic fragment and may further contain one other polypeptide of LASV; the GPC protein, a fragment of the GPC protein (such as GP1 or GP2), the NP protein and / or the mNP protein. In a preferred embodiment, the LASV VLP contains the Z protein or its antigenic fragment, and the GPC protein or its antigenic fragment, or a fragment of the GPC protein (such as GP1 and / or GP2). In another preferred embodiment, the LASV VLP contains the Z protein or its antigenic fragment, the GPC protein or its antigenic fragment, and the mNP protein or NP protein or its antigenic fragment.

[0140] In a preferred embodiment of the present invention, the recombinant measles virus expresses the GPC protein and the mNP protein of LASV. In another preferred embodiment of the present invention, the recombinant measles virus expresses the GPC protein and the Z protein of LASV.

[0141] Furthermore, according to some embodiments of the present invention, the recombinant measles virus also expresses at least one polypeptide or protein or antigenic fragment of the measles virus. In other words, the recombinant measles virus expresses at least one of the following polypeptides: the N protein, P protein, M protein, F protein, H protein and L protein of MeV.

[0142] According to this embodiment, the recombinant virus expresses recombinant antigenic particles of measles virus and Lassa virus, thereby allowing the induction of a cellular response, or a humoral response, or a cellular and humoral response against the polypeptides of LASV and against the polypeptides of MeV. In a particular embodiment of the present invention, inducing a cellular response includes inducing a T cell response, particularly a CD4+ and / or CD8+ T cell response.

[0143] Therefore, the present invention relates to a method for preparing recombinant infectious measles virus particles, the method comprising:

[0144] (a) Transfecting cells stably expressing T7 RNA polymerase and measles N and P proteins, particularly helper cells, particularly HEK293 helper cells, with the nucleic acid construct of the present invention or the transfer plasmid vector of the present invention;

[0145] (b) Maintain the transfected cells under conditions suitable for the production of recombinant measles virus and / or LASV VLPs;

[0146] (c) Infect cells capable of propagating recombinant measles virus and / or LASV VLPs by co-culturing with the transfected cells of step (b);

[0147] (d) Harvest recombinant measles virus and / or LASV VLPs, wherein the recombinant measles virus expresses at least one LASV protein, preferably at least the GPC protein and optionally the NP protein, mNP protein, and / or Z protein, preferably expressing the GPC protein and mNP protein; the LASV VLPs express at least the Z protein and may also express another LASV protein selected from the GPC protein, NP protein, and / or mNP protein.

[0148] According to a specific embodiment, the present invention relates to a method for preparing recombinant infectious measles virus particles, the method comprising:

[0149] a) Transfer, particularly transfect, the nucleic acid construct of the present invention or a transfer vector containing the nucleic acid construct in an auxiliary cell line, the auxiliary cell line also expressing proteins necessary for the transcription, replication, and encapsidation of the MeV antigenomic (+) RNA sequence from its cDNA under conditions permitting viral particle assembly, and

[0150] b) Recover recombinant infectious MeV-LASV virus expressing at least one polypeptide or protein of LASV or an antigenic fragment thereof.

[0151] According to a specific embodiment of the present invention, the method comprises:

[0152] a) Transfect an auxiliary cell with the nucleic acid construct of the present invention, with a transfer plasmid vector, wherein the auxiliary cell is capable of expressing auxiliary functions to express RNA polymerase and to express the N protein, P protein, and L protein of the MeV virus;

[0153] b) Co-culture the transfected auxiliary cells of step 1) with a passage cell suitable for the passage of a cDNA-derived MeV attenuated strain;

[0154] c) Recover recombinant infectious MeV-LASV virus expressing at least one polypeptide of LASV.

[0155] According to another specific embodiment of the present invention, the method for producing recombinant infectious MeV-LASV comprises:

[0156] a) Recombinant a cell or cell culture that stably produces RNA polymerase, the nucleoprotein (N) of measles virus, and the phosphoprotein (P) which is a polymerase cofactor of measles virus with the nucleic acid construct of the present invention and a vector containing a nucleic acid encoding the large protein (L) of measles virus RNA polymerase, and

[0157] b) Recover infectious MeV-LASV virus from the recombinant cell or recombinant cell culture.

[0158] According to a specific embodiment of the method, recombinant MeV is produced which expresses LASV proteins that at least include the GPC protein and / or LASV VLPs that at least include the Z protein, wherein the recombinant MeV and / or VLPs may express at least one other LASV protein or antigen or an antigenic fragment thereof, such as GPC or a fragment thereof, especially GP1 and / or GP2, and optionally the mNP of LASV. In other embodiments, the LASV VLPs include the Z protein or a fragment thereof, and optionally the GPC protein, and may include GP1 and / or GP2. In a preferred embodiment of the present invention, the LASV VLPs include the Z protein or an antigenic fragment thereof and the GPC protein or an antigenic fragment thereof. By way of illustration, the method for rescuing recombinant MeV that expresses LASV proteins (especially LASV VLPs) includes the following steps:

[0159] 1) Co-transfecting helper cells that stably express T7 RNA polymerase and the measles N protein and P protein, especially HEK293 helper cells, with (i) a transfer vector (especially a plasmid) and (ii) a vector (especially a plasmid) encoding the MeV L polymerase cDNA, the transfer vector containing a cDNA encoding the full-length antigenomic (+) RNA of measles virus, the cDNA being recombined with at least one polynucleotide encoding at least one LASV protein (such as a polynucleotide encoding the GPC protein, NP protein, mNP protein, and / or Z protein);

[0160] 2) Culturing the co-transfected helper cells under conditions capable of producing MV-LASV recombinant virus;

[0161] 3) Propagating the recombinant virus thus produced by co-culturing the helper cells of step 2) with cells capable of subsequent propagation, such as Vero cells;

[0162] 4) Recovering the replicated MeV-LASV recombinant virus and LASV proteins, especially LASV virus-like particles.

[0163] As used herein, "recombinant" means introducing at least one polynucleotide into a cell, for example in the form of a vector, the polynucleotide being (fully or partially) integrated or not integrated into the cell.

[0164] According to one specific embodiment, recombination can be obtained with a first polynucleotide which is the nucleic acid construct of the present invention. The recombination can also or alternatively comprise the introduction of a polynucleotide which is a vector encoding the large protein (L) of the RNA polymerase of measles virus, the definition, properties and stability of the expression of which have been described herein.

[0165] According to the present invention, a cell or cell line or cell culture stably producing the RNA polymerase, the nucleoprotein (N) of measles virus and the polymerase cofactor phosphoprotein (P) of measles virus is a cell or cell line or cell culture as defined in this specification, i.e., a recombinant cell which has also been transformed to some extent by the introduction of more than one polynucleotide as defined above. In a specific embodiment of the present invention, the cell or cell line or cell culture stably producing the RNA polymerase, the N protein and the P protein does not produce the L protein of measles virus or produces the L protein of measles virus unstably, for example, enabling transient expression or production thereof. The production of the recombinant MeV-LASV virus of the present invention can involve the transfer of the transformed cells as described herein. As used herein, "transfer" means plating the recombinant cells onto different types of cells, especially onto a monolayer of different types of cells. These latter cells are competent cells to maintain the replication and production of the infectious recombinant MeV-LASV virus, i.e., to form infectious virus inside the cells respectively and possibly release these infectious viruses outside the cells, while possibly releasing LASV immunogenic particles and / or LASV VLPs. This transfer results in the co-culture of the recombinant cells of the present invention with the competent cells as defined above.

[0166] When the recombinant cells are not an effective virus-producing culture, i.e., when the infectious recombinant MeV-LASV virus cannot be effectively recovered from these recombinant cells, the above transfer can be an additional, i.e., optional step. This step is introduced after further recombination of the recombinant cells of the present invention with any nucleic acid construct of the present invention and optionally a vector which contains a nucleic acid encoding the large protein (L) of the RNA polymerase of measles virus.

[0167] In a specific embodiment of the present invention, the transfer step is required because the recombinant cells, which are usually selected for their ease of recombination ability, are not efficient enough in maintaining and producing the recombinant infectious MeV-LASV virus. In the said embodiment, the cell or cell line or cell culture of step 1) of the above method is a recombinant cell or cell line or recombinant cell culture according to the present invention.

[0168] The cells suitable for preparing the recombinant cells of the present invention are prokaryotic or eukaryotic cells, particularly animal or plant cells, more particularly mammalian cells, such as human cells or non-human mammalian cells or avian cells or yeast cells. In a particular embodiment, the cells are isolated from a primary culture or cell line prior to recombination of the cell genome. The cells of the present invention can be dividing cells or non-dividing cells.

[0169] According to a preferred embodiment, the helper cells are derived from the human embryonic kidney cell line 293, which is deposited in the ATCC under the number CRL-1573. The specific cell line 293 is the cell line disclosed in WO2008 / 078198 and is referred to as 293T7 / N / P in the following examples. Thus, the present invention also relates to a host cell transfected or transformed with a nucleic acid construct according to any embodiment of the present invention, or transfected with a transfer plasmid vector, particularly an avian cell or a mammalian cell. Suitable cells are VERO NK cells (African green monkey kidney cells) and MRC5 cells (Medical Research Council cell strain 5). According to another aspect of the method, the cells suitable for subculture are CEF cells (chicken embryo fibroblasts). The CEF cells can be prepared from fertilized eggs obtained from EARL Morizeau (8 rue Moulin, 28190 Dangers, France) or any other producer of fertilized eggs.

[0170] The method disclosed according to the present invention is advantageously used for the production of an infectious replicating recombinant MeV-LASV virus suitable for use as an immunocomposition. Thus, the present invention relates to a composition, particularly an antigenic composition, the active ingredient of which comprises an infectious replicating recombinant MeV-LASV virus rescued from the nucleic acid construct of the present invention and particularly obtained by the disclosed method. The composition can be a vaccine composition for administration to a human in need thereof, particularly a child. The composition can be used for the treatment of LASV infection. The composition can be used to provide protection against LASV. Thus, the composition can be an immunogenic or antigenic composition for prophylactic or preventive treatment against LASV infection. In particular, the active component or active ingredient in the composition comprises recombinant MeV-LASV particles, which are rescued from the transfer plasmid vector according to the present invention and optionally in association with VLPs or antigenic fragments thereof comprising the Z protein of LASV and optionally other proteins. In the context of the present invention, the terms "associated" or "in association" mean that the recombinant MeV-LASV virus particles and the LASV polypeptides or proteins (particularly as VLPs) are generally present in a single composition in physically separate entities. In a specific embodiment of the present invention, the composition is a vaccine.

[0171] The present invention also relates to recombinant MeV-LASV infectious replicating virus particles, which are combined with LASV polypeptides or proteins, or antigenic fragments thereof, and possibly combined with LASV VLPs or any composition according to the present invention, and the particles are used for treating or preventing Lassa virus infection in a subject, particularly a human subject, especially a child.

[0172] The present invention also relates to the use of recombinant MeV-LASV infectious replicating virus and combined LASV polypeptides or proteins or antigenic fragments thereof, and possibly combined LASV VLPs in a dosing regimen and a dosage regimen, which particularly elicits an immune response, a favorable protective immune response, against a disease caused or induced by Lassa virus infection in a human subject, especially a child.

[0173] In a particular embodiment of the present invention, the composition or the use of the composition is capable of immunizing a subject, particularly a human subject, especially a child, after a single injection. In other words, the composition or the use of the composition may require a single administration of a selected dose of recombinant MeV-LASV infectious replicating virus. Alternatively, it may require multiple administrations in a prime-boost regimen. The priming and boosting can be achieved using the same active ingredients consisting of recombinant MeV-LASV infectious replicating virus and combined LASV polypeptides and proteins, or antigenic fragments thereof and / or LASV VLPs.

[0174] The present invention also relates to the assembly of different active ingredients, including recombinant MeV-LASV infectious replicating virus and combined LASV polypeptides or proteins and / or LASV VLPs as one of these ingredients. The assembly of the active ingredients is advantageously used for immunizing a host, particularly a human host.

[0175] The inventors have shown that administration of recombinant MeV-LASV infectious replicating virus elicits an immune response, particularly the production of neutralizing antibodies against LASV-related polypeptides. This shows that administration of the active ingredients of the present invention elicits host immunity. The vaccine of the present invention is safe and elicits an immune response in the host, particularly including CD4+ and CD8+ T cell responses. As shown in the examples, the vaccine of the present invention induces antigen-specific T cell responses. Additionally, it has been shown that immunized monkey hosts can survive after challenge with a lethal dose of LASV.

[0176] After immunizing the host and challenging with LASV, in the immunized monkey hosts, the levels of liver enzymes (ALT and AST), lactate dehydrogenase (LDH), C-reactive protein (CRP), and albumin remain normal or increase slightly, while these levels increase several-fold in non-immunized hosts.

[0177] The compositions of the present invention are capable of eliciting the production of recombinant LASV-specific immunoglobulins (particularly IgM and IgG) as well as neutralizing antibodies. The compositions of the present invention are safe vaccines, immunogenic and effective in a host. The compositions and their uses confer at least a T cell response in vaccinated hosts and can confer immunity against Lassa virus infection.

[0178] The compositions of the present invention are also capable of eliciting the production of MeV-specific immunoglobulins (particularly IgM and IgG) as well as neutralizing antibodies. The compositions of the present invention are safe vaccines, immunogenic and effective in a host. The compositions and their uses confer at least a T cell response in vaccinated hosts and can confer immunity against measles virus infection.

[0179] The compositions of the present invention also relate to recombinant MeV-LASV infectious replicating viruses and combined LASV polypeptides or proteins or antigenic fragments thereof, and the use of LASV VLPs, possibly in combination, in dosing and dosage regimens, which particularly elicit an immune response, a favorable protective immune response, against measles virus infection or induced diseases in human subjects, especially children.

[0180] The present invention also relates to recombinant MeV-LASV infectious replicating virus particles in combination with LASV polypeptides or proteins or antigenic fragments thereof and / or LASV VLPs or any composition of the present invention for treating or preventing measles virus infection in a subject, particularly a human subject, especially a child.

[0181] The present invention also relates to heterologous polynucleotides comprising any one of the codon-optimized sequences encoding the GPC protein, the Z protein, the NP protein, and / or the mNP protein. Accordingly, the present invention also relates to codon-optimized polynucleotides comprising SEQ ID No: 2, SEQ ID No: 4, SEQ ID No: 6, and / or SEQ ID No: 8 or codon-optimized polynucleotides consisting of SEQ ID No: 2, SEQ ID No: 4, SEQ ID No: 6, and / or SEQ ID No: 8. Sequence Listing <110> Institut Pasteur Centre National de la Recherche Scientifique (CNRS) <120> Lassa Vaccine <130> B12929A - AD / HLQ / KN <140> PCT / FRXX XXX XXX <141> December 20, 2018 <150> US 62 / 609155 <151> December 21, 2017 <160> 17 <170> PatentIn version 3.5 <210> 1 <211> 491 <212> PRT <213> Artificial Sequence <220> <223> Protein GPC <400> 1 Met Gly Gln Ile Val Thr Phe Phe Gln Glu Val Pro His Val Ile Glu 1 5 10 15 Glu Val Met Asn Ile Val Leu Ile Ala Leu Ser Val Leu Ala Val Leu 20 25 30 Lys Gly Leu Tyr Asn Phe Ala Thr Cys Gly Leu Val Gly Leu Val Thr 35 40 45 Phe Leu Leu Leu Cys Gly Arg Ser Cys Thr Thr Ser Leu Tyr Lys Gly 50 55 60 Val Tyr Glu Leu Gln Thr Leu Glu Leu Asn Met Glu Thr Leu Asn Met 65 70 75 80 Thr Met Pro Leu Ser Cys Thr Lys Asn Asn Ser His His Tyr Ile Met 85 90 95 Val Gly Asn Glu Thr Gly Leu Glu Leu Thr Leu Thr Asn Thr Ser Ile 100 105 110 Ile Asn His Lys Phe Cys Asn Leu Ser Asp Ala His Lys Lys Asn Leu 115 120 125 Tyr Asp His Ala Leu Met Ser Ile Ile Ser Thr Phe His Leu Ser Ile 130 135 140 Pro Asn Phe Asn Gln Tyr Glu Ala Met Ser Cys Asp Phe Asn Gly Gly 145 150 155 160 Lys Ile Ser Val Gln Tyr Asn Leu Ser His Ser Tyr Ala Gly Asp Ala 165 170 175 Ala Asn His Cys Gly Thr Val Ala Asn Gly Val Leu Gln Thr Phe Met 180 185 190 Arg Met Ala Trp Gly Gly Ser Tyr Ile Ala Leu Asp Ser Gly Arg Gly 195 200 205 Asn Trp Asp Cys Ile Met Thr Ser Tyr Gln Tyr Leu Ile Ile Gln Asn 210 215 220 Thr Thr Trp Glu Asp His Cys Gln Phe Ser Arg Pro Ser Pro Ile Gly 225 230 235 240 Tyr Leu Gly Leu Leu Ser Gln Arg Thr Arg Asp Ile Tyr Ile Ser Arg 245 250 255 Arg Leu Leu Gly Thr Phe Thr Trp Thr Leu Ser Asp Ser Glu Gly Lys 260 265 270 Asp Thr Pro Gly Gly Tyr Cys Leu Thr Arg Trp Met Leu Ile Glu Ala 275 280 285 Glu Leu Lys Cys Phe Gly Asn Thr Ala Val Ala Lys Cys Asn Glu Lys 290 295 300 His Asp Glu Glu Phe Cys Asp Met Leu Arg Leu Phe Asp Phe Asn Lys 305 310 315 320 Gln Ala Ile Gln Arg Leu Lys Ala Glu Ala Gln Met Ser Ile Gln Leu 325 330 335 Ile Asn Lys Ala Val Asn Ala Leu Ile Asn Asp Gln Leu Ile Met Lys 340 345 350 Asn His Leu Arg Asp Ile Met Gly Ile Pro Tyr Cys Asn Tyr Ser Lys 355 360 365 Tyr Trp Tyr Leu Asn His Thr Thr Thr Gly Arg Thr Ser Leu Pro Lys 370 375 380 Cys Trp Leu Val Ser Asn Gly Ser Tyr Leu Asn Glu Thr His Phe Ser 385 390 395 400 Asp Asp Ile Glu Gln Gln Ala Asp Asn Met Ile Thr Glu Met Leu Gln 405 410 415 Lys Glu Tyr Met Glu Arg Gln Gly Lys Thr Pro Leu Gly Leu Val Asp 420 425 430 Leu Phe Val Phe Ser Thr Ser Phe Tyr Leu Ile Ser Ile Phe Leu His 435 440 445 Leu Val Lys Ile Pro Thr His Arg His Ile Val Gly Lys Ser Cys Pro 450 455 460 Lys Pro His Arg Leu Asn His Met Gly Ile Cys Ser Cys Gly Leu Tyr 465 470 475 480 Lys Gln Pro Gly Val Pro Val Lys Trp Lys Arg 485 490 <210> 2 <211> 1476 <212> DNA <213> Artificial Sequence <220> <223> Codon-optimized cDNA GPC <400> 2 atgggccaga ttgtcacatt ctttcaggaa gtgccacacg tcattgagga ggtcatgaac 60 atcgtgctga ttgctctgtc agtgctggca gtgctgaaag gactgtacaa cttcgctacc 120 tgtggactgg tgggactggt cacattcctg ctgctgtgcg gcagaagttg cactacctca 180 ctgtacaaag gagtgtacga gctgcagact ctggaactga acatggagac actgaatatg 240 acaatgcctc tgagctgcac caagaataat agccaccact atatcatggt cgggaacgaa 300 accggcctgg aactgaccct gacaaacacc agcatcatta accacaagtt ctgcaatctg 360 agcgacgctc acaagaagaa cctgtatgac cacgctctga tgtccatcat cagtaccttt 420 cacctgtcca tccccaattt caaccagtac gaggcaatgt catgcgactt caacgggggc 480 aagatcagtg tccagtacaa cctgagccac tcctacgccg gcgacgcagc caaccactgc 540 ggaactgtcg ccaatggcgt gctgcagaca ttcatgagga tggcatgggg gggatcttac 600 atcgcactgg atagcggcag gggcaattgg gattgcatca tgacttccta tcagtatctg 660 attatccaga atactacatg ggaggatcat tgccagttca gtcggcccag ccctattgga 720 tatctggggc tgctgtcaca gagaacacgg gatatctata tttcaagacg cctgctgggc 780 acattcactt ggacactgtc agacagtgag ggcaaggata ctccaggggg ctactgcctg 840 acacgatgga tgctgatcga agcagagctg aaatgcttcg gcaataccgc agtggccaag 900 tgcaacgaga aacacgacga ggagttctgc gacatgctga ggctgttcga cttcaacaaa 960 caggctatcc agagactgaa ggcagaagcc cagatgtcaa tccagctgat caacaaggca 1020 gtgaacgccc tgatcaacga ccagctgatc atgaagaacc acctgagaga cattatgggc 1080 atcccctact gtaattacag caagtattgg tacctgaacc acactacaac cgggagaaca 1140 tccctgccca agtgctggct ggtcagcaat gggagttatc tgaatgaaac ccatttcagc 1200 gacgatatcg aacagcaggc tgacaacatg atcacagaga tgctgcagaa agagtacatg 1260 gaaagacagg gcaagacacc actgggactg gtcgatctgt tcgtcttctc cactagcttc 1320 tatctgattt ccatcttcct gcacctggtg aagatcccca ctcataggca cattgtcggc 1380 aagagttgcc ctaaacccca taggctgaat cacatgggga tttgtagttg cggcctgtat 1440 aagcagcctg gcgtgcctgt gaaatggaag agatga 1476 <210> 3 <211> 569 <212> PRT <213> Artificial Sequence <220> <223> Protein NP <400> 3 Met Ser Ala Ser Lys Glu Ile Lys Ser Phe Leu Trp Thr Gln Ser Leu 1 5 10 15 Arg Arg Glu Leu Ser Gly Tyr Cys Ser Asn Ile Lys Leu Gln Val Val 20 25 30 Lys Asp Ala Gln Ala Leu Leu His Gly Leu Asp Phe Ser Glu Val Ser 35 40 45 Asn Val Gln Arg Leu Met Arg Lys Glu Arg Arg Asp Asp Asn Asp Leu 50 55 60 Lys Arg Leu Arg Asp Leu Asn Gln Ala Val Asn Asn Leu Val Glu Leu 65 70 75 80 Lys Ser Thr Gln Gln Lys Ser Ile Leu Arg Val Gly Thr Leu Thr Ser 85 90 95 Asp Asp Leu Leu Ile Leu Ala Ala Asp Leu Glu Lys Leu Lys Ser Lys 100 105 110 Val Ile Arg Thr Glu Arg Pro Leu Ser Ala Gly Val Tyr Met Gly Asn 115 120 125 Leu Ser Ser Gln Gln Leu Asp Gln Arg Arg Ala Leu Leu Asn Met Ile 130 135 140 Gly Met Ser Gly Gly Asn Gln Gly Ala Arg Ala Gly Arg Asp Gly Val 145 150 155 160 Val Arg Val Trp Asp Val Lys Asn Ala Glu Leu Leu Asn Asn Gln Phe 165 170 175 Gly Thr Met Pro Ser Leu Thr Leu Ala Cys Leu Thr Lys Gln Gly Gln 180 185 190 Val Asp Leu Asn Asp Ala Val Gln Ala Leu Thr Asp Leu Gly Leu Ile 195 200 205 Tyr Thr Ala Lys Tyr Pro Asn Thr Ser Asp Leu Asp Arg Leu Thr Gln 210 215 220 Ser His Pro Ile Leu Asn Met Ile Asp Thr Lys Lys Ser Ser Leu Asn 225 230 235 240 Ile Ser Gly Tyr Asn Phe Ser Leu Gly Ala Ala Val Lys Ala Gly Ala 245 250 255 Cys Met Leu Asp Gly Gly Asn Met Leu Glu Thr Ile Lys Val Ser Pro 260 265 270 Gln Thr Met Asp Gly Ile Leu Lys Ser Ile Leu Lys Val Lys Lys Ala 275 280 285 Leu Gly Met Phe Ile Ser Asp Thr Pro Gly Glu Arg Asn Pro Tyr Glu 290 295 300 Asn Ile Leu Tyr Lys Ile Cys Leu Ser Gly Asp Gly Trp Pro Tyr Ile 305 310 315 320 Ala Ser Arg Thr Ser Ile Thr Gly Arg Ala Trp Glu Asn Thr Val Val 325 330 335 Asp Leu Glu Ser Asp Gly Lys Pro Gln Lys Ala Asp Ser Asn Asn Ser 340 345 350 Ser Lys Ser Leu Gln Ser Ala Gly Phe Thr Ala Gly Leu Thr Tyr Ser 355 360 365 Gln Leu Met Thr Leu Lys Asp Ala Met Leu Gln Leu Asp Pro Asn Ala 370 375 380 Lys Thr Trp Met Asp Ile Glu Gly Arg Pro Glu Asp Pro Val Glu Ile 385 390 395 400 Ala Leu Tyr Gln Pro Ser Ser Gly Cys Tyr Ile His Phe Phe Arg Glu 405 410 415 Pro Thr Asp Leu Lys Gln Phe Lys Gln Asp Ala Lys Tyr Ser His Gly 420 425 430 Ile Asp Val Thr Asp Leu Phe Ala Thr Gln Pro Gly Leu Thr Ser Ala 435 440 445 Val Ile Asp Ala Leu Pro Arg Asn Met Val Ile Thr Cys Gln Gly Ser 450 455 460 Asp Asp Ile Arg Lys Leu Leu Glu Ser Gln Gly Arg Lys Asp Ile Lys 465 470 475 480 Leu Ile Asp Ile Ala Leu Ser Lys Thr Asp Ser Arg Lys Tyr Glu Asn 485 490 495 Ala Val Trp Asp Gln Tyr Lys Asp Leu Cys His Met His Thr Gly Val 500 505 510 Val Val Glu Lys Lys Lys Arg Gly Gly Lys Glu Glu Ile Thr Pro His 515 520 525 Cys Ala Leu Met Asp Cys Ile Met Phe Asp Ala Ala Val Ser Gly Gly 530 535 540 Leu Asn Thr Ser Val Leu Arg Ala Val Leu Pro Arg Asp Met Val Phe 545 550 555 560 Arg Thr Ser Thr Pro Arg Val Val Leu 565 <210> 4 <211> 1710 <212> DNA <213> Artificial Sequence <220> <223> Codon-optimized cDNA NP <400> 4 atgagtgcca gcaaagaaat caagagcttc ctgtggaccc agagtctgcg gagggaactg 60 agcggatact gtagcaacat caaactgcag gtggtcaagg acgctcaggc actgctgcat 120 gggctggact tctccgaggt gtctaatgtg cagcggctga tgcggaaaga acggagggac 180 gataatgacc tgaagcgact gcgcgacctg aaccaggcag tgaacaatct ggtcgagctg 240 aagagcaccc agcagaaatc aatcctgcgg gtcgggacac tgacatctga cgacctgctg 300 atcctggctg cagacctgga gaagctgaaa tcgaaagtga tccgcaccga aaggccactg 360 tccgccgggg tctacatggg caatctgtct tcccagcagc tggaccagag gcgggctctg 420 ctgaacatga ttgggatgtc cggaggaaat cagggagcta gagccgggag ggacggagtc 480 gtgcgggtct gggacgtgaa gaatgccgaa ctgctgaaca accagttcgg gaccatgcca 540 agtctgacac tggcatgcct gactaaacag ggccaggtgg atctgaatga tgcagtccag 600 gctctgaccg acctgggcct gatctacacc gccaagtacc ccaatactag cgacctggat 660 agactgaccc agagccaccc catcctgaac atgatcgaca ctaagaagtc ctcactgaac 720 atcagtggct ataatttctc cctgggggca gcagtcaagg ctggcgcatg catgctggac 780 ggcgggaata tgctggaaac catcaaagtg tctccccaga ccatggatgg catcctgaaa 840 tctattctga aagtcaagaa ggccctggga atgtttattt cagacacccc cggcgagagg 900 aatccatatg agaacattct gtataagatt tgcctgagtg gcgacgggtg gccatacatt 960 gcaagccgga catcaattac cggaagagct tgggagaata cagtcgtgga cctggaaagc 1020 gcaagccgga catcaattac cggaagagct tgggagaata cagtcgtgga cctggaaagc 1020 gacggcaagc cccagaaggc cgactcaaac aactcctcaa agagtctgca gtcagctggc 1080 gacggcaagc cccagaaggc cgactcaaac aactcctcaa agagtctgca gtcagctggc 1080 ttcacagcag ggctgactta ctcccagctg atgacactga aggacgcaat gctgcagctg 1140 ttcacagcag ggctgactta ctcccagctg atgacactga aggacgcaat gctgcagctg 1140 gacccaaacg ctaagacatg gatggacatc gagggacggc cagaagatcc agtggaaatc 1200 gacccaaacg ctaagacatg gatggacatc gagggacggc cagaagatcc agtggaaatc 1200 gcactgtatc agccatcatc cggatgctat atccatttct tccgggaacc aactgatctg 1260 gcactgtatc agccatcatc cggatgctat atccatttct tccgggaacc aactgatctg 1260 aagcagttca agcaggatgc aaagtactcc cacggaatcg atgtcaccga tctgttcgca 1320 aagcagttca agcaggatgc aaagtactcc cacggaatcg atgtcaccga tctgttcgca 1320 acccagccag gactgacatc agccgtcatc gatgccctgc ctaggaacat ggtcattact 1380 acccagccag gactgacatc agccgtcatc gatgccctgc ctaggaacat ggtcattact 1380 tgccagggct ccgacgatat taggaagctg ctggagagcc agggacggaa ggatatcaaa 1440 tgccagggct ccgacgatat taggaagctg ctggagagcc agggacggaa ggatatcaaa 1440 ctgatcgata ttgccctgtc taagactgat agccggaaat atgagaatgc agtctgggat 1500 ctgatcgata ttgccctgtc taagactgat agccggaaat atgagaatgc agtctgggat 1500 cagtacaagg acctgtgcca tatgcatacc ggagtggtcg tcgagaagaa gaagaggggc 1560 cagtacaagg acctgtgcca tatgcatacc ggagtggtcg tcgagaagaa gaagaggggc 1560 ggaaaggaag agatcacacc ccactgtgcc ctgatggatt gcatcatgtt cgacgcagcc 1620 ggaaaggaag agatcacacc ccactgtgcc ctgatggatt gcatcatgtt cgacgcagcc 1620 gtgtccgggg gcctgaacac ctcagtcctg agggctgtcc tgccaagaga tatggtgttt 1680 gtgtccgggg gcctgaacac ctcagtcctg agggctgtcc tgccaagaga tatggtgttt 1680 agaacttcaa ccccaagagt cgtcctgtaa 1710 <210> 5 <211> 569 <212> PRT <213> Artificial Sequence <220> <223> Mutant protein NP <400> 5 Met Ser Ala Ser Lys Glu Ile Lys Ser Phe Leu Trp Thr Gln Ser Leu 1 5 10 15 Arg Arg Glu Leu Ser Gly Tyr Cys Ser Asn Ile Lys Leu Gln Val Val 20 25 30 Lys Asp Ala Gln Ala Leu Leu His Gly Leu Asp Phe Ser Glu Val Ser 35 40 45 Asn Val Gln Arg Leu Met Arg Lys Glu Arg Arg Asp Asp Asn Asp Leu 50 55 60 Lys Arg Leu Arg Asp Leu Asn Gln Ala Val Asn Asn Leu Val Glu Leu 65 70 75 80 Lys Ser Thr Gln Gln Lys Ser Ile Leu Arg Val Gly Thr Leu Thr Ser 85 90 95 Asp Asp Leu Leu Ile Leu Ala Ala Asp Leu Glu Lys Leu Lys Ser Lys 100 105 110 Val Ile Arg Thr Glu Arg Pro Leu Ser Ala Gly Val Tyr Met Gly Asn 115 120 125 Leu Ser Ser Gln Gln Leu Asp Gln Arg Arg Ala Leu Leu Asn Met Ile 130 135 140 Gly Met Ser Gly Gly Asn Gln Gly Ala Arg Ala Gly Arg Asp Gly Val 145 150 155 160 Val Arg Val Trp Asp Val Lys Asn Ala Glu Leu Leu Asn Asn Gln Phe 165 170 175 Gly Thr Met Pro Ser Leu Thr Leu Ala Cys Leu Thr Lys Gln Gly Gln 180 185 190 Val Asp Leu Asn Asp Ala Val Gln Ala Leu Thr Asp Leu Gly Leu Ile 195 200 205 Tyr Thr Ala Lys Tyr Pro Asn Thr Ser Asp Leu Asp Arg Leu Thr Gln 210 215 220 Ser His Pro Ile Leu Asn Met Ile Asp Thr Lys Lys Ser Ser Leu Asn 225 230 235 240 Ile Ser Gly Tyr Asn Phe Ser Leu Gly Ala Ala Val Lys Ala Gly Ala 245 250 255 Cys Met Leu Asp Gly Gly Asn Met Leu Glu Thr Ile Lys Val Ser Pro 260 265 270 Gln Thr Met Asp Gly Ile Leu Lys Ser Ile Leu Lys Val Lys Lys Ala 275 280 285 Leu Gly Met Phe Ile Ser Asp Thr Pro Gly Glu Arg Asn Pro Tyr Glu 290 295 300 Asn Ile Leu Tyr Lys Ile Cys Leu Ser Gly Asp Gly Trp Pro Tyr Ile 305 310 315 320 Ala Ser Arg Thr Ser Ile Thr Gly Arg Ala Trp Glu Asn Thr Val Val 325 330 335 Asp Leu Glu Ser Asp Gly Lys Pro Gln Lys Ala Asp Ser Asn Asn Ser 340 345 350 Ser Lys Ser Leu Gln Ser Ala Gly Phe Thr Ala Gly Leu Thr Tyr Ser 355 360 365 Gln Leu Met Thr Leu Lys Asp Ala Met Leu Gln Leu Asp Pro Asn Ala 370 375 380 Lys Thr Trp Met Ala Ile Glu Ala Arg Pro Glu Asp Pro Val Glu Ile 385 390 395 400 Ala Leu Tyr Gln Pro Ser Ser Gly Cys Tyr Ile His Phe Phe Arg Glu 405 410 415 Pro Thr Asp Leu Lys Gln Phe Lys Gln Asp Ala Lys Tyr Ser His Gly 420 425 430 Ile Asp Val Thr Asp Leu Phe Ala Thr Gln Pro Gly Leu Thr Ser Ala 435 440 445 Val Ile Asp Ala Leu Pro Arg Asn Met Val Ile Thr Cys Gln Gly Ser 450 455 460 Asp Asp Ile Arg Lys Leu Leu Glu Ser Gln Gly Arg Lys Asp Ile Lys 465 470 475 480 Leu Ile Asp Ile Ala Leu Ser Lys Thr Asp Ser Arg Lys Tyr Glu Asn 485 490 495 Ala Val Trp Asp Gln Tyr Lys Asp Leu Cys His Met His Thr Gly Val 500 505 510 Val Val Glu Lys Lys Lys Arg Gly Gly Lys Glu Glu Ile Thr Pro His 515 520 525 Cys Ala Leu Met Asp Cys Ile Met Phe Asp Ala Ala Val Ser Gly Gly 530 535 540 Leu Asn Thr Ser Val Leu Arg Ala Val Leu Pro Arg Asp Met Val Phe 545 550 555 560 Arg Thr Ser Thr Pro Arg Val Val Leu 565 <210> 6 <211> 1710 <212> DNA <213> Artificial Sequence <220> <223> Codon-optimized cDNA mutant NP <400> 6 atgagtgcca gcaaagaaat caagagcttc ctgtggaccc agagtctgcg gagggaactg 60 agcggatact gtagcaacat caaactgcag gtggtcaagg acgctcaggc actgctgcat 120 gggctggact tctccgaggt gtctaatgtg cagcggctga tgcggaaaga acggagggac 180 gataatgacc tgaagcgact gcgcgacctg aaccaggcag tgaacaatct ggtcgagctg 240 aagagcaccc agcagaaatc aatcctgcgg gtcgggacac tgacatctga cgacctgctg 300 atcctggctg cagacctgga gaagctgaaa tcgaaagtga tccgcaccga aaggccactg 360 tccgccgggg tctacatggg caatctgtct tcccagcagc tggaccagag gcgggctctg 420 ctgaacatga ttgggatgtc cggaggaaat cagggagcta gagccgggag ggacggagtc 480 gtgcgggtct gggacgtgaa gaatgccgaa ctgctgaaca accagttcgg gaccatgcca 540 agtctgacac tggcatgcct gactaaacag ggccaggtgg atctgaatga tgcagtccag 600 gctctgaccg acctgggcct gatctacacc gccaagtacc ccaatactag cgacctggat 660 agactgaccc agagccaccc catcctgaac atgatcgaca ctaagaagtc ctcactgaac 720 atcagtggct ataatttctc cctgggggca gcagtcaagg ctggcgcatg catgctggac 780 ggcgggaata tgctggaaac catcaaagtg tctccccaga ccatggatgg catcctgaaa 840 tctattctga aagtcaagaa ggccctggga atgtttattt cagacacccc cggcgagagg 900 aatccatatg agaacattct gtataagatt tgcctgagtg gcgacgggtg gccatacatt 960 gcaagccgga catcaattac cggaagagct tgggagaata cagtcgtgga cctggaaagc 1020 gacggcaagc cccagaaggc cgactcaaac aactcctcaa agagtctgca gtcagctggc 1080 ttcacagcag ggctgactta ctcccagctg atgacactga aggacgcaat gctgcagctg 1140 gacccaaacg ctaagacatg gatggccatc gaggcccggc cagaagatcc agtggaaatc 1200 gcactgtatc agccatcatc cggatgctat atccatttct tccgggaacc aactgatctg 1260 aagcagttca agcaggatgc aaagtactcc cacggaatcg atgtcaccga tctgttcgca 1320 acccagccag gactgacatc agccgtcatc gatgccctgc ctaggaacat ggtcattact 1380 tgccagggct ccgacgatat taggaagctg ctggagagcc agggacggaa ggatatcaaa 1440 ctgatcgata ttgccctgtc taagactgat agccggaaat atgagaatgc agtctgggat 1500 cagtacaagg acctgtgcca tatgcatacc ggagtggtcg tcgagaagaa gaagaggggc 1560 ggaaaggaag agatcacacc ccactgtgcc ctgatggatt gcatcatgtt cgacgcagcc 1620 gtgtccgggg gcctgaacac ctcagtcctg agggctgtcc tgccaagaga tatggtgttt 1680 agaacttcaa ccccaagagt cgtcctgtaa 1710 <210> 7 <211> 99 <212> PRT <213> Artificial Sequence <220> <223> Protein Z <400> 7 Met Gly Asn Lys Gln Ala Lys Ala Pro Glu Ser Lys Asp Ser Pro Arg 1 5 10 15 Ala Ser Leu Ile Pro Asp Ala Thr His Leu Gly Pro Gln Phe Cys Lys 20 25 30 Ser Cys Trp Phe Glu Asn Lys Gly Leu Val Glu Cys Asn Asn His Tyr 35 40 45 Leu Cys Leu Asn Cys Leu Thr Leu Leu Leu Ser Val Ser Asn Arg Cys 50 55 60 Pro Ile Cys Lys Met Pro Leu Pro Thr Lys Leu Arg Pro Ser Ala Ala 65 70 75 80 Pro Thr Ala Pro Pro Thr Gly Ala Ala Asp Ser Ile Arg Pro Pro Pro 85 90 95 Tyr Ser Pro <210> 8 <211> 300 <212> DNA <213> Artificial Sequence <220> <223> Codon-optimized cDNA Z <400> 8 atgggcaata agcaggcaaa ggcacccgaa agcaaggatt cacctagagc atcactgatt 60 cccgacgcaa ctcatctggg gccacagttc tgcaaatcct gttggttcga gaacaaaggc 120 ctggtggagt gcaataacca ctacctgtgc ctgaactgtc tgacactgct gctgagtgtg 180 agcaacagat gcccaatctg caagatgcct ctgccaacaa agctgaggcc ttctgctgca 240 cccaccgcac caccaactgg agccgcagac agcattagac cccccccata ctcaccataa 300 <210> 9 <211> 20551 <212> DNA <213> Artificial Sequence <220> <223> Plasmid MeV-GPC <400> 9 gcggccgcta atacgactca ctatagggcc aactttgttt ggtctgatga gtccgtgagg 60 acgaaacccg gagtcccggg tcaccaaaca aagttgggta aggatagttc aatcaatgat 120 catcttctag tgcacttagg attcaagatc ctattatcag ggacaagagc aggattaggg 180 atatccgaga tggccacact tttaaggagc ttagcattgt tcaaaagaaa caaggacaaa 240 ccacccatta catcaggatc cggtggagcc atcagaggaa tcaaacacat tattatagta 300 ccaatccctg gagattcctc aattaccact cgatccagac ttctggaccg gttggtgagg 360 ttaattggaa acccggatgt gagcgggccc aaactaacag gggcactaat aggtatatta 420 tccttatttg tggagtctcc aggtcaattg attcagagga tcaccgatga ccctgacgtt 480 agcataaggc tgttagaggt tgtccagagt gaccagtcac aatctggcct taccttcgca 540 tcaagaggta ccaacatgga ggatgaggcg gaccaatact tttcacatga tgatccaatt 600 agtagtgatc aatccaggtt cggatggttc gggaacaagg aaatctcaga tattgaagtg 660 caagaccctg agggattcaa catgattctg ggtaccatcc tagcccaaat ttgggtcttg 720 ctcgcaaagg cggttacggc cccagacacg gcagctgatt cggagctaag aaggtggata 780 aagtacaccc aacaaagaag ggtagttggt gaatttagat tggagagaaa atggttggat 840 gtggtgagga acaggattgc cgaggacctc tccttacgcc gattcatggt cgctctaatc 900 ctggatatca agagaacacc cggaaacaaa cccaggattg ctgaaatgat atgtgacatt 960 gatacatata tcgtagaggc aggattagcc agttttatcc tgactattaa gtttgggata 1020 gaaactatgt atcctgctct tggactgcat gaatttgctg gtgagttatc cacacttgag 1080 tccttgatga acctttacca gcaaatgggg gaaactgcac cctacatggt aatcctggag 1140 aactcaattc agaacaagtt cagtgcagga tcataccctc tgctctggag ctatgccatg 1200 ggagtaggag tggaacttga aaactccatg ggaggtttga actttggccg atcttacttt 1260 gatccagcat attttagatt agggcaagag atggtaagga ggtcagctgg aaaggtcagt 1320 tccacattgg catctgaact cggtatcact gccgaggatg caaggcttgt ttcagagatt 1380 gcaatgcata ctactgagga caagatcagt agagcggttg gacccagaca agcccaagta 1440 tcatttctac acggtgatca aagtgagaat gagctaccga gattgggggg caaggaagat 1500 aggagggtca aacagagtcg aggagaagcc agggagagct acagagaaac cgggcccagc 1560 agagcaagtg atgcgagagc tgcccatctt ccaaccggca cacccctaga cattgacact 1620 gcaacggagt ccagccaaga tccgcaggac agtcgaaggt cagctgacgc cctgcttagg 1680 ctgcaagcca tggcaggaat ctcggaagaa caaggctcag acacggacac ccctatagtg 1740 tacaatgaca gaaatcttct agactaggtg cgagaggccg agggccagaa caacatccgc 1800 ctaccatcca tcattgttat aaaaaactta ggaaccaggt ccacacagcc gccagcccat 1860 caaccatcca ctcccacgat tggagccaat ggcagaagag caggcacgcc atgtcaaaaa 1920 cggactggaa tgcatccggg ctctcaaggc cgagcccatc ggctcactgg ccatcgagga 1980 agctatggca gcatggtcag aaatatcaga caacccagga caggagcgag ccacctgcag 2040 ggaagagaag gcaggcagtt cgggtctcag caaaccatgc ctctcagcaa ttggatcaac 2100 tgaaggcggt gcacctcgca tccgcggtca gggacctgga gagagcgatg acgacgctga 2160 aactttggga atccccccaa gaaatctcca ggcatcaagc actgggttac agtgttatta 2220 cgtttatgat cacagcggtg aagcggttaa gggaatccaa gatgctgact ctatcatggt 2280 tcaatcaggc cttgatggtg atagcaccct ctcaggagga gacaatgaat ctgaaaacag 2340 cgatgtggat attggcgaac ctgataccga gggatatgct atcactgacc ggggatctgc 2400 tcccatctct atggggttca gggcttctga tgttgaaact gcagaaggag gggagatcca 2460 cgagctcctg agactccaat ccagaggcaa caactttccg aagcttggga aaactctcaa 2520 tgttcctccg cccccggacc ccggtagggc cagcacttcc gggacaccca ttaaaaaggg 2580 cacagacgcg agattagcct catttggaac ggagatcgcg tctttattga caggtggtgc 2640 aacccaatgt gctcgaaagt caccctcgga accatcaggg ccaggtgcac ctgcggggaa 2700 tgtccccgag tgtgtgagca atgccgcact gatacaggag tggacacccg aatctggtac 2760 cacaatctcc ccgagatccc agaataatga agaaggggga gactattatg atgatgagct 2820 gttctctgat gtccaagata ttaaaacagc cttggccaaa atacacgagg ataatcagaa 2880 gataatctcc aagctagaat cactgctgtt attgaaggga gaagttgagt caattaagaa 2940 gcagatcaac aggcaaaata tcagcatatc caccctggaa ggacacctct caagcatcat 3000 gatcgccatt cctggacttg ggaaggatcc caacgacccc actgcagatg tcgaaatcaa 3060 tcccgacttg aaacccatca taggcagaga ttcaggccga gcactggccg aagttctcaa 3120 gaaacccgtt gccagccgac aactccaagg aatgacaaat ggacggacca gttccagagg 3180 acagctgctg aaggaatttc agctaaagcc gatcgggaaa aagatgagct cagccgtcgg 3240 gtttgttcct gacaccggcc ctgcatcacg cagtgtaatc cgctccatta taaaatccag 3300 ccggctagag gaggatcgga agcgttacct gatgactctc cttgatgata tcaaaggagc 3360 caatgatctt gccaagttcc accagatgct gatgaagata ataatgaagt agctacagct 3420 caacttacct gccaacccca tgccagtcga cccaactagc ctaccctcca tcattgttat 3480 aaaaaactta ggaaccaggt ccacacagcc gccagcccat caacgcgtac gatgggccag 3540 attgtcacat tctttcagga agtgccacac gtcattgagg aggtcatgaa catcgtgctg 3600 attgctctgt cagtgctggc agtgctgaaa ggactgtaca acttcgctac ctgtggactg 3660 gtgggactgg tcacattcct gctgctgtgc ggcagaagtt gcactacctc actgtacaaa 3720 ggagtgtacg agctgcagac tctggaactg aacatggaga cactgaatat gacaatgcct 3780 ctgagctgca ccaagaataa tagccaccac tatatcatgg tcgggaacga aaccggcctg 3840 gaactgaccc tgacaaacac cagcatcatt aaccacaagt tctgcaatct gagcgacgct 3900 cacaagaaga acctgtatga ccacgctctg atgtccatca tcagtacctt tcacctgtcc 3960 atccccaatt tcaaccagta cgaggcaatg tcatgcgact tcaacggggg caagatcagt 4020 gtccagtaca acctgagcca ctcctacgcc ggcgacgcag ccaaccactg cggaactgtc 4080 gccaatggcg tgctgcagac attcatgagg atggcatggg ggggatctta catcgcactg 4140 gatagcggca ggggcaattg ggattgcatc atgacttcct atcagtatct gattatccag 4200 aatactacat gggaggatca ttgccagttc agtcggccca gccctattgg atatctgggg 4260 ctgctgtcac agagaacacg ggatatctat atttcaagac gcctgctggg cacattcact 4320 tggacactgt cagacagtga gggcaaggat actccagggg gctactgcct gacacgatgg 4380 atgctgatcg aagcagagct gaaatgcttc ggcaataccg cagtggccaa gtgcaacgag 4440 aaacacgacg aggagttctg cgacatgctg aggctgttcg acttcaacaa acaggctatc 4500 cagagactga aggcagaagc ccagatgtca atccagctga tcaacaaggc agtgaacgcc 4560 ctgatcaacg accagctgat catgaagaac cacctgagag acattatggg catcccctac 4620 tgtaattaca gcaagtattg gtacctgaac cacactacaa ccgggagaac atccctgccc 4680 aagtgctggc tggtcagcaa tgggagttat ctgaatgaaa cccatttcag cgacgatatc 4740 gaacagcagg ctgacaacat gatcacagag atgctgcaga aagagtacat ggaaagacag 4800 ggcaagacac cactgggact ggtcgatctg ttcgtcttct ccactagctt ctatctgatt 4860 tccatcttcc tgcacctggt gaagatcccc actcataggc acattgtcgg caagagttgc 4920 cctaaacccc ataggctgaa tcacatgggg atttgtagtt gcggcctgta taagcagcct 4980 ggcgtgcctg tgaaatggaa gagatgagcg cgcagcgctt agacgtctcg cgatcgatac 5040 tagtacaacc taaatccatt ataaaaaact taggagcaaa gtgattgcct cccaaggtcc 5100 acaatgacag agacctacga cttcgacaag tcggcatggg acatcaaagg gtcgatcgct 5160 ccgatacaac ccaccaccta cagtgatggc aggctggtgc cccaggtcag agtcatagat 5220 cctggtctag gcgacaggaa ggatgaatgc tttatgtaca tgtttctgct gggggttgtt 5280 gaggacagcg attccctagg gcctccaatc gggcgagcat ttgggttcct gcccttaggt 5340 gttggcagat ccacagcaaa gcccgaaaaa ctcctcaaag aggccactga gcttgacata 5400 gttgttagac gtacagcagg gctcaatgaa aaactggtgt tctacaacaa caccccacta 5460 actctcctca caccttggag aaaggtccta acaacaggga gtgtcttcaa cgcaaaccaa 5520 gtgtgcaatg cggttaatct gataccgctc gataccccgc agaggttccg tgttgtttat 5580 atgagcatca cccgtctttc ggataacggg tattacaccg ttcctagaag aatgctggaa 5640 ttcagatcgg tcaatgcagt ggccttcaac ctgctggtga cccttaggat tgacaaggcg 5700 ataggccctg ggaagatcat cgacaataca gagcaacttc ctgaggcaac atttatggtc 5760 cacatcggga acttcaggag aaagaagagt gaagtctact ctgccgatta ttgcaaaatg 5820 aaaatcgaaa agatgggcct ggtttttgca cttggtggga tagggggcac cagtcttcac 5880 attagaagca caggcaaaat gagcaagact ctccatgcac aactcgggtt caagaagacc 5940 ttatgttacc cgctgatgga tatcaatgaa gaccttaatc gattactctg gaggagcaga 6000 tgcaagatag taagaatcca ggcagttttg cagccatcag ttcctcaaga attccgcatt 6060 tacgacgacg tgatcataaa tgatgaccaa ggactattca aagttctgta gaccgtagtg 6120 cccagcaatg cccgaaaacg acccccctca caatgacagc cagaaggccc ggacaaaaaa 6180 gccccctccg aaagactcca cggaccaagc gagaggccag ccagcagccg acggcaagcg 6240 cgaacaccag gcggccccag cacagaacag ccctgacaca aggccaccac cagccacccc 6300 aatctgcatc ctcctcgtgg gacccccgag gaccaacccc caaggctgcc cccgatccaa 6360 accaccaacc gcatccccac cacccccggg aaagaaaccc ccagcaattg gaaggcccct 6420 ccccctcttc ctcaacacaa gaactccaca accgaaccgc acaagcgacc gaggtgaccc 6480 aaccgcaggc atccgactcc ctagacagat cctctctccc cggcaaacta aacaaaactt 6540 agggccaagg aacatacaca cccaacagaa cccagacccc ggcccacggc gccgcgcccc 6600 caacccccga caaccagagg gagcccccaa ccaatcccgc cggctccccc ggtgcccaca 6660 ggcagggaca ccaacccccg aacagaccca gcacccaacc atcgacaatc caagacgggg 6720 gggccccccc aaaaaaaggc ccccaggggc cgacagccag caccgcgagg aagcccaccc 6780 accccacaca cgaccacggc aaccaaacca gaacccagac caccctgggc caccagctcc 6840 cagactcggc catcaccccg cagaaaggaa aggccacaac ccgcgcaccc cagccccgat 6900 ccggcgggga gccacccaac ccgaaccagc acccaagagc gatccccgaa ggacccccga 6960 accgcaaagg acatcagtat cccacagcct ctccaagtcc cccggtctcc tcctcttctc 7020 gaagggacca aaagatcaat ccaccacacc cgacgacact caactcccca cccctaaagg 7080 agacaccggg aatcccagaa tcaagactca tccaatgtcc atcatgggtc tcaaggtgaa 7140 cgtctctgcc atattcatgg cagtactgtt aactctccaa acacccaccg gtcaaatcca 7200 ttggggcaat ctctctaaga taggggtggt aggaatagga agtgcaagct acaaagttat 7260 gactcgttcc agccatcaat cattagtcat aaaattaatg cccaatataa ctctcctcaa 7320 taactgcacg agggtagaga ttgcagaata caggagacta ctgagaacag ttttggaacc 7380 aattagagat gcacttaatg caatgaccca gaatataaga ccggttcaga gtgtagcttc 7440 aagtaggaga cacaagagat ttgcgggagt agtcctggca ggtgcggccc taggcgttgc 7500 cacagctgct cagataacag ccggcattgc acttcaccag tccatgctga actctcaagc 7560 catcgacaat ctgagagcga gcctggaaac tactaatcag gcaattgaga caatcagaca 7620 agcagggcag gagatgatat tggctgttca gggtgtccaa gactacatca ataatgagct 7680 gataccgtct atgaaccaac tatcttgtga tttaatcggc cagaagctcg ggctcaaatt 7740 gctcagatac tatacagaaa tcctgtcatt atttggcccc agtttacggg accccatatc 7800 tgcggagata tctatccagg ctttgagcta tgcgcttgga ggagacatca ataaggtgtt 7860 agaaaagctc ggatacagtg gaggtgattt actgggcatc ttagagagcg gaggaataaa 7920 ggcccggata actcacgtcg acacagagtc ctacttcatt gtcctcagta tagcctatcc 7980 gacgctgtcc gagattaagg gggtgattgt ccaccggcta gagggggtct cgtacaacat 8040 aggctctcaa gagtggtata ccactgtgcc caagtatgtt gcaacccaag ggtaccttat 8100 ctcgaatttt gatgagtcat cgtgtacttt catgccagag gggactgtgt gcagccaaaa 8160 tgccttgtac ccgatgagtc ctctgctcca agaatgcctc cgggggtaca ccaagtcctg 8220 tgctcgtaca ctcgtatccg ggtcttttgg gaaccggttc attttatcac aagggaacct 8280 aatagccaat tgtgcatcaa tcctttgcaa gtgttacaca acaggaacga tcattaatca 8340 agaccctgac aagatcctaa catacattgc tgccgatcac tgcccggtag tcgaggtgaa 8400 cggcgtgacc atccaagtcg ggagcaggag gtatccagac gctgtgtact tgcacagaat 8460 tgacctcggt cctcccatat cattggagag gttggacgta gggacaaatc tggggaatgc 8520 aattgctaag ttggaggatg ccaaggaatt gttggagtca tcggaccaga tattgaggag 8580 tatgaaaggt ttatcgagca ctagcatagt ctacatcctg attgcagtgt gtcttggagg 8640 gttgataggg atccccgctt taatatgttg ctgcaggggg cgttgtaaca aaaagggaga 8700 acaagttggt atgtcaagac caggcctaaa gcctgatctt acgggaacat caaaatccta 8760 tgtaaggtcg ctctgatcct ctacaactct tgaaacacaa atgtcccaca agtctcctct 8820 tcgtcatcaa gcaaccaccg cacccagcat caagcccacc tgaaattatc tccggcttcc 8880 ctctggccga acaatatcgg tagttaatca aaacttaggg tgcaagatca tccacaatgt 8940 caccacaacg agaccggata aatgccttct acaaagataa cccccatccc aagggaagta 9000 ggatagtcat taacagagaa catcttatga ttgatagacc ttatgttttg ctggctgttc 9060 tgtttgtcat gtttctgagc ttgatcgggt tgctagccat tgcaggcatt agacttcatc 9120 gggcagccat ctacaccgca gagatccata aaagcctcag caccaatcta gatgtaacta 9180 actcaatcga gcatcaggtc aaggacgtgc tgacaccact cttcaaaatc atcggtgatg 9240 aagtgggcct gaggacacct cagagattca ctgacctagt gaaattaatc tctgacaaga 9300 ttaaattcct taatccggat agggagtacg acttcagaga tctcacttgg tgtatcaacc 9360 cgccagagag aatcaaattg gattatgatc aatactgtgc agatgtggct gctgaagagc 9420 tcatgaatgc attggtgaac tcaactctac tggagaccag aacaaccaat cagttcctag 9480 ctgtctcaaa gggaaactgc tcagggccca ctacaatcag aggtcaattc tcaaacatgt 9540 cgctgtccct gttagacttg tatttaggtc gaggttacaa tgtgtcatct atagtcacta 9600 tgacatccca gggaatgtat gggggaactt acctagtgga aaagcctaat ctgagcagca 9660 aaaggtcaga gttgtcacaa ctgagcatgt accgagtgtt tgaagtaggt gttatcagaa 9720 atccgggttt gggggctccg gtgttccata tgacaaacta tcttgagcaa ccagtcagta 9780 atgatctcag caactgtatg gtggctttgg gggagctcaa actcgcagcc ctttgtcacg 9840 gggaagattc tatcacaatt ccctatcagg gatcagggaa aggtgtcagc ttccagctcg 9900 tcaagctagg tgtctggaaa tccccaaccg acatgcaatc ctgggtcccc ttatcaacgg 9960 atgatccagt gatagacagg ctttacctct catctcacag aggtgttatc gctgacaatc 10020 aagcaaaatg ggctgtcccg acaacacgaa cagatgacaa gttgcgaatg gagacatgct 10080 tccaacaggc gtgtaagggt aaaatccaag cactctgcga gaatcccgag tgggcaccat 10140 tgaaggataa caggattcct tcatacgggg tcttgtctgt tgatctgagt ctgacagttg 10200 agcttaaaat caaaattgct tcgggattcg ggccattgat cacacacggt tcagggatgg 10260 acctatacaa atccaaccac aacaatgtgt attggctgac tatcccgcca atgaagaacc 10320 tagccttagg tgtaatcaac acattggagt ggataccgag attcaaggtt agtccctacc 10380 tcttcactgt cccaattaag gaagcaggcg aagactgcca tgccccaaca tacctacctg 10440 cggaggtgga tggtgatgtc aaactcagtt ccaatctggt gattctacct ggtcaagatc 10500 tccaatatgt tttggcaacc tacgatactt ccagggttga acatgctgtg gtttattacg 10560 tttacagccc aagccgctca ttttcttact tttatccttt taggttgcct ataaaggggg 10620 tccccatcga attacaagtg gaatgcttca catgggacca aaaactctgg tgccgtcact 10680 tctgtgtgct tgcggactca gaatctggtg gacatatcac tcactctggg atggtgggca 10740 tgggagtcag ctgcacagtc acccgggaag atggaaccaa tcgcagatag ggctgctagt 10800 gaaccaatca catgatgtca cccagacatc aggcataccc actagtgtga aatagacatc 10860 agaattaaga aaaacgtagg gtccaagtgg ttccccgtta tggactcgct atctgtcaac 10920 cagatcttat accctgaagt tcacctagat agcccgatag ttaccaataa gatagtagcc 10980 atcctggagt atgctcgagt ccctcacgct tacagcctgg aggaccctac actgtgtcag 11040 aacatcaagc accgcctaaa aaacggattt tccaaccaaa tgattataaa caatgtggaa 11100 gttgggaatg tcatcaagtc caagcttagg agttatccgg cccactctca tattccatat 11160 ccaaattgta atcaggattt atttaacata gaagacaaag agtcaacgag gaagatccgt 11220 gaactcctca aaaaggggaa ttcgctgtac tccaaagtca gtgataaggt tttccaatgc 11280 ttaagggaca ctaactcacg gcttggccta ggctccgaat tgagggagga catcaaggag 11340 aaagttatta acttgggagt ttacatgcac agctcccagt ggtttgagcc ctttctgttt 11400 tggtttacag tcaagactga gatgaggtca gtgattaaat cacaaaccca tacttgccat 11460 aggaggagac acacacctgt attcttcact ggtagttcag ttgagttgct aatctctcgt 11520 gaccttgttg ctataatcag taaagagtct caacatgtat attacctgac atttgaactg 11580 gttttgatgt attgtgatgt catagagggg aggttaatga cagagaccgc tatgactatt 11640 gatgctaggt atacagagct tctaggaaga gtcagataca tgtggaaact gatagatggt 11700 ttcttccctg cactcgggaa tccaacttat caaattgtag ccatgctgga gcctctttca 11760 cttgcttacc tgcagctgag ggatataaca gtagaactca gaggtgcttt ccttaaccac 11820 tgctttactg aaatacatga tgttcttgac caaaacgggt tttctgatga aggtacttat 11880 catgagttaa ctgaagctct agattacatt ttcataactg atgacataca tctgacaggg 11940 gagattttct catttttcag aagtttcggc caccccagac ttgaagcagt aacggctgct 12000 gaaaatgtta ggaaatacat gaatcagcct aaagtcattg tgtatgagac tctgatgaaa 12060 ggtcatgcca tattttgtgg aatcataatc aacggctatc gtgacaggca cggaggcagt 12120 tggccaccgc tgaccctccc cctgcatgct gcagacacaa tccggaatgc tcaagcttca 12180 ggtgaagggt taacacatga gcagtgcgtt gataactgga aatcttttgc tggagtgaaa 12240 tttggctgct ttatgcctct tagcctggat agtgatctga caatgtacct aaaggacaag 12300 gcacttgctg ctctccaaag ggaatgggat tcagtttacc cgaaagagtt cctgcgttac 12360 gaccctccca agggaaccgg gtcacggagg cttgtagatg ttttccttaa tgattcgagc 12420 tttgacccat atgatgtgat aatgtatgtt gtaagtggag cttacctcca tgaccctgag 12480 ttcaacctgt cttacagcct gaaagaaaag gagatcaagg aaacaggtag actttttgct 12540 aaaatgactt acaaaatgag ggcatgccaa gtgattgctg aaaatctaat ctcaaacggg 12600 attggcaaat attttaagga caatgggatg gccaaggatg agcacgattt gactaaggca 12660 ctccacactc tagctgtctc aggagtcccc aaagatctca aagaaagtca cagggggggg 12720 ccagtcttaa aaacctactc ccgaagccca gtccacacaa gtaccaggaa cgtgagagca 12780 gcaaaagggt ttatagggtt ccctcaagta attcggcagg accaagacac tgatcatccg 12840 gagaatatgg aagcttacga gacagtcagt gcatttatca cgactgatct caagaagtac 12900 tgccttaatt ggagatatga gaccatcagc ttgtttgcac agaggctaaa tgagatttac 12960 ggattgccct catttttcca gtggctgcat aagaggcttg agacctctgt cctgtatgta 13020 agtgaccctc attgcccccc cgaccttgac gcccatatcc cgttatataa agtccccaat 13080 gatcaaatct tcattaagta ccctatggga ggtatagaag ggtattgtca gaagctgtgg 13140 accatcagca ccattcccta tctatacctg gctgcttatg agagcggagt aaggattgct 13200 tcgttagtgc aaggggacaa tcagaccata gccgtaacaa aaagggtacc cagcacatgg 13260 ccctacaacc ttaagaaacg ggaagctgct agagtaacta gagattactt tgtaattctt 13320 aggcaaaggc tacatgatat tggccatcac ctcaaggcaa atgagacaat tgtttcatca 13380 catttttttg tctattcaaa aggaatatat tatgatgggc tacttgtgtc ccaatcactc 13440 aagagcatcg caagatgtgt attctggtca gagactatag ttgatgaaac aagggcagca 13500 tgcagtaata ttgctacaac aatggctaaa agcatcgaga gaggttatga ccgttacctt 13560 gcatattccc tgaacgtcct aaaagtgata cagcaaattc tgatctctct tggcttcaca 13620 atcaattcaa ccatgacccg ggatgtagtc atacccctcc tcacaaacaa cgacctctta 13680 ataaggatgg cactgttgcc cgctcctatt ggggggatga attatctgaa tatgagcagg 13740 ctgtttgtca gaaacatcgg tgatccagta acatcatcaa ttgctgatct caagagaatg 13800 attctcgcct cactaatgcc tgaagagacc ctccatcaag taatgacaca acaaccgggg 13860 gactcttcat tcctagactg ggctagcgac ccttactcag caaatcttgt atgtgtccag 13920 agcatcacta gactcctcaa gaacataact gcaaggtttg tcctgatcca tagtccaaac 13980 ccaatgttaa aaggattatt ccatgatgac agtaaagaag aggacgaggg actggcggca 14040 ttcctcatgg acaggcatat tatagtacct agggcagctc atgaaatcct ggatcatagt 14100 gtcacagggg caagagagtc tattgcaggc atgctggata ccacaaaagg cttgattcga 14160 gccagcatga ggaagggggg gttaacctct cgagtgataa ccagattgtc caattatgac 14220 tatgaacaat tcagagcagg gatggtgcta ttgacaggaa gaaagagaaa tgtcctcatt 14280 gacaaagagt catgttcagt gcagctggcg agagctctaa gaagccatat gtgggcgagg 14340 ctagctcgag gacggcctat ttacggcctt gaggtccctg atgtactaga atctatgcga 14400 ggccacctta ttcggcgtca tgagacatgt gtcatctgcg agtgtggatc agtcaactac 14460 ggatggtttt ttgtcccctc gggttgccaa ctggatgata ttgacaagga aacatcatcc 14520 ttgagagtcc catatattgg ttctaccact gatgagagaa cagacatgaa gcttgccttc 14580 gtaagagccc caagtcgatc cttgcgatct gctgttagaa tagcaacagt gtactcatgg 14640 gcttacggtg atgatgatag ctcttggaac gaagcctggt tgttggctag gcaaagggcc 14700 aatgtgagcc tggaggagct aagggtgatc actcccatct caacttcgac taatttagcg 14760 cataggttga gggatcgtag cactcaagtg aaatactcag gtacatccct tgtccgagtg 14820 gcgaggtata ccacaatctc caacgacaat ctctcatttg tcatatcaga taagaaggtt 14880 gatactaact ttatatacca acaaggaatg cttctagggt tgggtgtttt agaaacattg 14940 tttcgactcg agaaagatac cggatcatct aacacggtat tacatcttca cgtcgaaaca 15000 gattgttgcg tgatcccgat gatagatcat cccaggatac ccagctcccg caagctagag 15060 ctgagggcag agctatgtac caacccattg atatatgata atgcaccttt aattgacaga 15120 gatgcaacaa ggctatacac ccagagccat aggaggcacc ttgtggaatt tgttacatgg 15180 tccacacccc aactatatca cattttagct aagtccacag cactatctat gattgacctg 15240 gtaacaaaat ttgagaagga ccatatgaat gaaatttcag ctctcatagg ggatgacgat 15300 atcaatagtt tcataactga gtttctgctc atagagccaa gattattcac tatctacttg 15360 ggccagtgtg cggccatcaa ttgggcattt gatgtacatt atcatagacc atcagggaaa 15420 tatcagatgg gtgagctgtt gtcatcgttc ctttctagaa tgagcaaagg agtgtttaag 15480 gtgcttgtca atgctctaag ccacccaaag atctacaaga aattctggca ttgtggtatt 15540 atagagccta tccatggtcc ttcacttgat gctcaaaact tgcacacaac tgtgtgcaac 15600 atggtttaca catgctatat gacctacctc gacctgttgt tgaatgaaga gttagaagag 15660 ttcacatttc tcttgtgtga aagcgacgag gatgtagtac cggacagatt cgacaacatc 15720 caggcaaaac acttatgtgt tctggcagat ttgtactgtc aaccagggac ctgcccacca 15780 attcgaggtc taagaccggt agagaaatgt gcagttctaa ccgaccatat caaggcagag 15840 gctatgttat ctccagcagg atcttcgtgg aacataaatc caattattgt agaccattac 15900 tcatgctctc tgacttatct ccggcgagga tcgatcaaac agataagatt gagagttgat 15960 ccaggattca ttttcgacgc cctcgctgag gtaaatgtca gtcagccaaa gatcggcagc 16020 aacaacatct caaatatgag catcaaggct ttcagacccc cacacgatga tgttgcaaaa 16080 ttgctcaaag atatcaacac aagcaagcac aatcttccca tttcaggggg caatctcgcc 16140 aattatgaaa tccatgcttt ccgcagaatc gggttgaact catctgcttg ctacaaagct 16200 gttgagatat caacattaat taggagatgc cttgagccag gggaggacgg cttgttcttg 16260 ggtgagggat cgggttctat gttgatcact tataaagaga tacttaaact aaacaagtgc 16320 ttctataata gtggggtttc cgccaattct agatctggtc aaagggaatt agcaccctat 16380 ccctccgaag ttggccttgt cgaacacaga atgggagtag gtaatattgt caaagtgctc 16440 ccctccgaag ttggccttgt cgaacacaga atgggagtag gtaatattgt caaagtgctc 16440 tttaacggga ggcccgaagt cacgtgggta ggcagtgtag attgcttcaa tttcatagtt 16500 tttaacggga ggcccgaagt cacgtgggta ggcagtgtag attgcttcaa tttcatagtt 16500 agtaatatcc ctacctctag tgtggggttt atccattcag atatagagac cttgcctgac 16560 agtaatatcc ctacctctag tgtggggttt atccattcag atatagagac cttgcctgac 16560 aaagatacta tagagaagct agaggaattg gcagccatct tatcgatggc tctgctcctg 16620 aaagatacta tagagaagct agaggaattg gcagccatct tatcgatggc tctgctcctg 16620 ggcaaaatag gatcaatact ggtgattaag cttatgcctt tcagcgggga ttttgttcag 16680 ggcaaaatag gatcaatact ggtgattaag cttatgcctt tcagcgggga ttttgttcag 16680 ggatttataa gttatgtagg gtctcattat agagaagtga accttgtata ccctagatac 16740 ggatttataa gttatgtagg gtctcattat agagaagtga accttgtata ccctagatac 16740 agcaacttca tctctactga atcttatttg gttatgacag atctcaaggc taaccggcta 16800 agcaacttca tctctactga atcttatttg gttatgacag atctcaaggc taaccggcta 16800 atgaatcctg aaaagattaa gcagcagata attgaatcat ctgtgaggac ttcacctgga 16860 atgaatcctg aaaagattaa gcagcagata attgaatcat ctgtgaggac ttcacctgga 16860 cttataggtc acatcctatc cattaagcaa ctaagctgca tacaagcaat tgtgggagac 16920 cttataggtc acatcctatc cattaagcaa ctaagctgca tacaagcaat tgtgggagac 16920 gcagttagta gaggtgatat caatcctact ctgaaaaaac ttacacctat agagcaggtg 16980 gcagttagta gaggtgatat caatcctact ctgaaaaaac ttacacctat agagcaggtg 16980 ctgatcaatt gcgggttggc aattaacgga cctaagctgt gcaaagaatt gatccaccat 17040 ctgatcaatt gcgggttggc aattaacgga cctaagctgt gcaaagaatt gatccaccat 17040 gatgttgcct cagggcaaga tggattgctt aattctatac tcatcctcta cagggagttg 17100 gcaagattca aagacaacca aagaagtcaa caagggatgt tccacgctta ccccgtattg 17160 gtaagtagca ggcaacgaga acttatatct aggatcaccc gcaaattctg ggggcacatt 17220 cttctttact ccgggaacaa aaagttgata aataagttta tccagaatct caagtccggc 17280 tatctgatac tagacttaca ccagaatatc ttcgttaaga atctatccaa gtcagagaaa 17340 cagattatta tgacgggggg tttgaaacgt gagtgggttt ttaaggtaac agtcaaggag 17400 accaaagaat ggtataagtt agtcggatac agtgccctga ttaaggacta attggttgaa 17460 ctccggaacc ctaatcctgc cctaggtggt taggcattat ttgcaatata ttaaagaaaa 17520 ctttgaaaat acgaagtttc tattcccagc tttgtctggt ggccggcatg gtcccagcct 17580 cctcgctggc gccggctggg caacattccg aggggaccgt cccctcggta atggcgaatg 17640 ggacgcggcc gatccggctg ctaacaaagc ccgaaaggaa gctgagttgg ctgctgccac 17700 cgctgagcaa taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt 17760 gctgaaagga ggaactatat ccggatgcgg ccgcgggccc tatggtaccc agcttttgtt 17820 gctgaaagga ggaactatat ccggatgcgg ccgcgggccc tatggtaccc agcttttgtt 17820 ccctttagtg agggttaatt ccgagcttgg cgtaatcatg gtcatagctg tttcctgtgt 17880 ccctttagtg agggttaatt ccgagcttgg cgtaatcatg gtcatagctg tttcctgtgt 17880 gaaattgtta tccgctcaca attccacaca acataggagc cggaagcata aagtgtaaag 17940 gaaattgtta tccgctcaca attccacaca acataggagc cggaagcata aagtgtaaag 17940 cctggggtgc ctaatgagtg aggtaactca cattaattgc gttgcgctca ctgcccgctt 18000 cctggggtgc ctaatgagtg aggtaactca cattaattgc gttgcgctca ctgcccgctt 18000 tccagtcggg aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag 18060 tccagtcggg aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag 18060 gcggtttgcg tattgggcgc tcttccgctt cctcgctcac tgactcgctg cgctcggtcg 18120 gcggtttgcg tattgggcgc tcttccgctt cctcgctcac tgactcgctg cgctcggtcg 18120 ttcggctgcg gcgagcggta tcagctcact caaaggcggt aatacggtta tccacagaat 18180 ttcggctgcg gcgagcggta tcagctcact caaaggcggt aatacggtta tccacagaat 18180 caggggataa cgcaggaaag aacatgtgag caaaaggcca gcaaaaggcc aggaaccgta 18240 caggggataa cgcaggaaag aacatgtgag caaaaggcca gcaaaaggcc aggaaccgta 18240 aaaaggccgc gttgctggcg tttttccata ggctcggccc ccctgacgag catcacaaaa 18300 aaaaggccgc gttgctggcg tttttccata ggctcggccc ccctgacgag catcacaaaa 18300 atcgacgctc aagtcagagg tggcgaaacc cgacaggact ataaagatac caggcgttcc 18360 atcgacgctc aagtcagagg tggcgaaacc cgacaggact ataaagatac caggcgttcc 18360 cccctggaag ctccctcgtg cgctctcctg ttccgaccct gccgcttacc ggatacctgt 18420 cccctggaag ctccctcgtg cgctctcctg ttccgaccct gccgcttacc ggatacctgt 18420 ccgcctttct cccttcggga agcgtggcgc tttctcaatg ctcacgctgt aggtatctca 18480 gttcggtgta ggtcgttcgc tccaagctgg gctgtgtgca cgaacccccc gttcagcccg 18540 accgctgcgc cttatccggt aactatcgtc ttgagtccaa cccggtaaga cacgacttat 18600 cgccactggc agcagccact ggtaacagga ttagcagagc gaggtatgta ggcggtgcta 18660 cagagttctt gaagtggtgg cctaactacg gctacactag aaggacagta tttggtatct 18720 gcgctctgct gaagccagtt accttcggaa aaagagttgg tagctcttga tccggcaaac 18780 aaaccaccgc tggtagcggt ggtttttttg tttgcaagca gcagattacg cgcagaaaaa 18840 aaggatctca agaagatcct ttgatctttt ctacggggtc tgacgctcag tggaacgaaa 18900 actcacgtta agggattttg gtcatgagat tatcaaaaag gatcttcacc tagatccttt 18960 taaattaaaa atgaagtttt aaatcaatct aaagtatata tgagtaaact tggtctgaca 19020 gttaccaatg cttaatcagt gaggcaccta tctcagcgat ctgtctattt cgttcatcca 19080 tagttgcctg actgcccgtc gtgtagataa ctacgatacg ggagggctta ccatctggcc 19140 ccagtgctgc aatgataccg cgagacccac gctcaccggc tccagattta tcagcaataa 19200 ccagtgctgc aatgataccg cgagacccac gctcaccggc tccagattta tcagcaataa 19200 accagccagc cggaagggcc gagcgcagaa gtggtcctgc aactttatcc gcctccatcc 19260 accagccagc cggaagggcc gagcgcagaa gtggtcctgc aactttatcc gcctccatcc 19260 agtctattaa ttgttgccgg gaagctagag taagtagttc gccagttaat agtttgcgca 19320 agtctattaa ttgttgccgg gaagctagag taagtagttc gccagttaat agtttgcgca 19320 acgttgttgc cattgctaca ggcatcgtgg tgtcacgctc gtcgtttggt atggcttcat 19380 acgttgttgc cattgctaca ggcatcgtgg tgtcacgctc gtcgtttggt atggcttcat 19380 tcagctccgg ttcccaacga tcaaggcgag ttacatgatc ccccatgttg tgaaaaaaag 19440 tcagctccgg ttcccaacga tcaaggcgag ttacatgatc ccccatgttg tgaaaaaaag 19440 cggttagctc cttcggtcct ccgatcgttg tcagaagtaa gttggccgca gtgttatcac 19500 cggttagctc cttcggtcct ccgatcgttg tcagaagtaa gttggccgca gtgttatcac 19500 tcatgcttat ggcagcactg cataattctc ttactgtcat gccatccgta agatgctttt 19560 tcatgcttat ggcagcactg cataattctc ttactgtcat gccatccgta agatgctttt 19560 ctgtgactgg tgagtactca accaagtcat tctgagaata gtgtatgcgg cgaccgagtt 19620 ctgtgactgg tgagtactca accaagtcat tctgagaata gtgtatgcgg cgaccgagtt 19620 gctcttgccc ggcgtcaata cgggataata ccgcgccaca tagcagaact ttaaaagtgc 19680 gctcttgccc ggcgtcaata cgggataata ccgcgccaca tagcagaact ttaaaagtgc 19680 tcatcattgg aaaacgttct tcggggcgaa aactctcaag gatcttaccg ctgttgagat 19740 tcatcattgg aaaacgttct tcggggcgaa aactctcaag gatcttaccg ctgttgagat 19740 ccagttcgat gtaacccact cgtgcaccca actgatcttc agcatctttt actttcacca 19800 ccagttcgat gtaacccact cgtgcaccca actgatcttc agcatctttt actttcacca 19800 gcgtttctgg gtgagcaaaa acaggaaggc aaaatgccgc aaaaaaggga ataagggcga 19860 cacggaaatg ttgaatactc atactcttcc tttttcaata ttattgaagc atttatcagg 19920 gttattgtct catgagcgga tacatatttg aatgtattta gaaaaataaa caaatagggg 19980 ttccgcgcac atttccccga aaagtgccac ctgaaattgt aaacgttaat attttgttaa 20040 aattcgcgtt aaatttttgt taaatcagct cattttttaa ccaataggcc gaaatcggca 20100 aaatccctta taaatcaaaa gaatagaccg agatagggtt gagtgttgtt ccagtttgga 20160 acaagagtcc actattaaag aacgtggact ccaacgtcaa agggcgaaaa accgtctatc 20220 agggcgatgg cccactacgt gaaccatcac cctaatcaag ttttttgggg tcgaggtgcc 20280 gtaaagcact aaatcggaac cctaaaggga gcccccgatt tagagcttga cggggaaagc 20340 cggcgaacgt ggcgagaaag gaagggaaga aagcgaaagg agcgggcgct agggcgctgg 20400 caagtgtagc ggtcacgctg cgcgtaacca ccacacccgc cgcgcttaat gcgccgctac 20460 agggcgcgtc ccattcgcca ttcaggctgc gcaactgttg ggaagggcga tcggtgcggg 20520 cctcttcgct attacgccag ccaccgcggt g 20551 <210> 10 <211> 22405 <212> DNA <213> Artificial Sequence <220> <223> Plasmid MeV-NP+GPC <400> 10 gcggccgcta atacgactca ctatagggcc aactttgttt ggtctgatga gtccgtgagg 60 acgaaacccg gagtcccggg tcaccaaaca aagttgggta aggatagttc aatcaatgat 120 catcttctag tgcacttagg attcaagatc ctattatcag ggacaagagc aggattaggg 180 atatccgaga tggccacact tttaaggagc ttagcattgt tcaaaagaaa caaggacaaa 240 ccacccatta catcaggatc cggtggagcc atcagaggaa tcaaacacat tattatagta 300 ccaatccctg gagattcctc aattaccact cgatccagac ttctggaccg gttggtgagg 360 ttaattggaa acccggatgt gagcgggccc aaactaacag gggcactaat aggtatatta 420 tccttatttg tggagtctcc aggtcaattg attcagagga tcaccgatga ccctgacgtt 480 agcataaggc tgttagaggt tgtccagagt gaccagtcac aatctggcct taccttcgca 540 tcaagaggta ccaacatgga ggatgaggcg gaccaatact tttcacatga tgatccaatt 600 agtagtgatc aatccaggtt cggatggttc gggaacaagg aaatctcaga tattgaagtg 660 caagaccctg agggattcaa catgattctg ggtaccatcc tagcccaaat ttgggtcttg 720 ctcgcaaagg cggttacggc cccagacacg gcagctgatt cggagctaag aaggtggata 780 aagtacaccc aacaaagaag ggtagttggt gaatttagat tggagagaaa atggttggat 840 gtggtgagga acaggattgc cgaggacctc tccttacgcc gattcatggt cgctctaatc 900 ctggatatca agagaacacc cggaaacaaa cccaggattg ctgaaatgat atgtgacatt 960 gatacatata tcgtagaggc aggattagcc agttttatcc tgactattaa gtttgggata 1020 gaaactatgt atcctgctct tggactgcat gaatttgctg gtgagttatc cacacttgag 1080 tccttgatga acctttacca gcaaatgggg gaaactgcac cctacatggt aatcctggag 1140 aactcaattc agaacaagtt cagtgcagga tcataccctc tgctctggag ctatgccatg 1200 ggagtaggag tggaacttga aaactccatg ggaggtttga actttggccg atcttacttt 1260 gatccagcat attttagatt agggcaagag atggtaagga ggtcagctgg aaaggtcagt 1320 tccacattgg catctgaact cggtatcact gccgaggatg caaggcttgt ttcagagatt 1380 gcaatgcata ctactgagga caagatcagt agagcggttg gacccagaca agcccaagta 1440 tcatttctac acggtgatca aagtgagaat gagctaccga gattgggggg caaggaagat 1500 aggagggtca aacagagtcg aggagaagcc agggagagct acagagaaac cgggcccagc 1560 agagcaagtg atgcgagagc tgcccatctt ccaaccggca cacccctaga cattgacact 1620 gcaacggagt ccagccaaga tccgcaggac agtcgaaggt cagctgacgc cctgcttagg 1680 ctgcaagcca tggcaggaat ctcggaagaa caaggctcag acacggacac ccctatagtg 1740 tacaatgaca gaaatcttct agactaggtg cgagaggccg agggccagaa caacatccgc 1800 ctaccatcca tcattgttat aaaaaactta ggaaccaggt ccacacagcc gccagcccat 1860 caaccatcca ctcccacgat tggagccaat ggcagaagag caggcacgcc atgtcaaaaa 1920 cggactggaa tgcatccggg ctctcaaggc cgagcccatc ggctcactgg ccatcgagga 1980 agctatggca gcatggtcag aaatatcaga caacccagga caggagcgag ccacctgcag 2040 ggaagagaag gcaggcagtt cgggtctcag caaaccatgc ctctcagcaa ttggatcaac 2100 tgaaggcggt gcacctcgca tccgcggtca gggacctgga gagagcgatg acgacgctga 2160 aactttggga atccccccaa gaaatctcca ggcatcaagc actgggttac agtgttatta 2220 cgtttatgat cacagcggtg aagcggttaa gggaatccaa gatgctgact ctatcatggt 2280 tcaatcaggc cttgatggtg atagcaccct ctcaggagga gacaatgaat ctgaaaacag 2340 cgatgtggat attggcgaac ctgataccga gggatatgct atcactgacc ggggatctgc 2400 tcccatctct atggggttca gggcttctga tgttgaaact gcagaaggag gggagatcca 2460 cgagctcctg agactccaat ccagaggcaa caactttccg aagcttggga aaactctcaa 2520 tgttcctccg cccccggacc ccggtagggc cagcacttcc gggacaccca ttaaaaaggg 2580 cacagacgcg agattagcct catttggaac ggagatcgcg tctttattga caggtggtgc 2640 aacccaatgt gctcgaaagt caccctcgga accatcaggg ccaggtgcac ctgcggggaa 2700 tgtccccgag tgtgtgagca atgccgcact gatacaggag tggacacccg aatctggtac 2760 cacaatctcc ccgagatccc agaataatga agaaggggga gactattatg atgatgagct 2820 gttctctgat gtccaagata ttaaaacagc cttggccaaa atacacgagg ataatcagaa 2880 gataatctcc aagctagaat cactgctgtt attgaaggga gaagttgagt caattaagaa 2940 gcagatcaac aggcaaaata tcagcatatc caccctggaa ggacacctct caagcatcat 3000 gatcgccatt cctggacttg ggaaggatcc caacgacccc actgcagatg tcgaaatcaa 3060 tcccgacttg aaacccatca taggcagaga ttcaggccga gcactggccg aagttctcaa 3120 gaaacccgtt gccagccgac aactccaagg aatgacaaat ggacggacca gttccagagg 3180 acagctgctg aaggaatttc agctaaagcc gatcgggaaa aagatgagct cagccgtcgg 3240 gtttgttcct gacaccggcc ctgcatcacg cagtgtaatc cgctccatta taaaatccag 3300 ccggctagag gaggatcgga agcgttacct gatgactctc cttgatgata tcaaaggagc 3360 caatgatctt gccaagttcc accagatgct gatgaagata ataatgaagt agctacagct 3420 caacttacct gccaacccca tgccagtcga cccaactagc ctaccctcca tcattgttat 3480 aaaaaactta ggaaccaggt ccacacagcc gccagcccat caacgcgtac gatgagtgcc 3540 agcaaagaaa tcaagagctt cctgtggacc cagagtctgc ggagggaact gagcggatac 3600 tgtagcaaca tcaaactgca ggtggtcaag gacgctcagg cactgctgca tgggctggac 3660 ttctccgagg tgtctaatgt gcagcggctg atgcggaaag aacggaggga cgataatgac 3720 ctgaagcgac tgcgcgacct gaaccaggca gtgaacaatc tggtcgagct gaagagcacc 3780 cagcagaaat caatcctgcg ggtcgggaca ctgacatctg acgacctgct gatcctggct 3840 gcagacctgg agaagctgaa atcgaaagtg atccgcaccg aaaggccact gtccgccggg 3900 gtctacatgg gcaatctgtc ttcccagcag ctggaccaga ggcgggctct gctgaacatg 3960 attgggatgt ccggaggaaa tcagggagct agagccggga gggacggagt cgtgcgggtc 4020 tgggacgtga agaatgccga actgctgaac aaccagttcg ggaccatgcc aagtctgaca 4080 ctggcatgcc tgactaaaca gggccaggtg gatctgaatg atgcagtcca ggctctgacc 4140 gacctgggcc tgatctacac cgccaagtac cccaatacta gcgacctgga tagactgacc 4200 cagagccacc ccatcctgaa catgatcgac actaagaagt cctcactgaa catcagtggc 4260 tataatttct ccctgggggc agcagtcaag gctggcgcat gcatgctgga cggcgggaat 4320 atgctggaaa ccatcaaagt gtctccccag accatggatg gcatcctgaa atctattctg 4380 aaagtcaaga aggccctggg aatgtttatt tcagacaccc ccggcgagag gaatccatat 4440 gagaacattc tgtataagat ttgcctgagt ggcgacgggt ggccatacat tgcaagccgg 4500 acatcaatta ccggaagagc ttgggagaat acagtcgtgg acctggaaag cgacggcaag 4560 ccccagaagg ccgactcaaa caactcctca aagagtctgc agtcagctgg cttcacagca 4620 gggctgactt actcccagct gatgacactg aaggacgcaa tgctgcagct ggacccaaac 4680 gctaagacat ggatggacat cgagggacgg ccagaagatc cagtggaaat cgcactgtat 4740 cagccatcat ccggatgcta tatccatttc ttccgggaac caactgatct gaagcagttc 4800 aagcaggatg caaagtactc ccacggaatc gatgtcaccg atctgttcgc aacccagcca 4860 ggactgacat cagccgtcat cgatgccctg cctaggaaca tggtcattac ttgccagggc 4920 tccgacgata ttaggaagct gctggagagc cagggacgga aggatatcaa actgatcgat 4980 attgccctgt ctaagactga tagccggaaa tatgagaatg cagtctggga tcagtacaag 5040 gacctgtgcc atatgcatac cggagtggtc gtcgagaaga agaagagggg cggaaaggaa 5100 gagatcacac cccactgtgc cctgatggat tgcatcatgt tcgacgcagc cgtgtccggg 5160 ggcctgaaca cctcagtcct gagggctgtc ctgccaagag atatggtgtt tagaacttca 5220 accccaagag tcgtcctgta attcgaacta cagctcaact tacctgccaa ccccatgcca 5280 gtcgacccaa ctagtacaac ctaaatccat tataaaaaac ttaggaacca ggtccacaca 5340 gccgccagcc catcaaccat ccactcccac gattggaggc cggccatggg ccagattgtc 5400 acattctttc aggaagtgcc acacgtcatt gaggaggtca tgaacatcgt gctgattgct 5460 ctgtcagtgc tggcagtgct gaaaggactg tacaacttcg ctacctgtgg actggtggga 5520 ctggtcacat tcctgctgct gtgcggcaga agttgcacta cctcactgta caaaggagtg 5580 tacgagctgc agactctgga actgaacatg gagacactga atatgacaat gcctctgagc 5640 tgcaccaaga ataatagcca ccactatatc atggtcggga acgaaaccgg cctggaactg 5700 accctgacaa acaccagcat cattaaccac aagttctgca atctgagcga cgctcacaag 5760 aagaacctgt atgaccacgc tctgatgtcc atcatcagta cctttcacct gtccatcccc 5820 aatttcaacc agtacgaggc aatgtcatgc gacttcaacg ggggcaagat cagtgtccag 5880 tacaacctga gccactccta cgccggcgac gcagccaacc actgcggaac tgtcgccaat 5940 ggcgtgctgc agacattcat gaggatggca tgggggggat cttacatcgc actggatagc 6000 ggcaggggca attgggattg catcatgact tcctatcagt atctgattat ccagaatact 6060 acatgggagg atcattgcca gttcagtcgg cccagcccta ttggatatct ggggctgctg 6120 tcacagagaa cacgggatat ctatatttca agacgcctgc tgggcacatt cacttggaca 6180 ctgtcagaca gtgagggcaa ggatactcca gggggctact gcctgacacg atggatgctg 6240 atcgaagcag agctgaaatg cttcggcaat accgcagtgg ccaagtgcaa cgagaaacac 6300 gacgaggagt tctgcgacat gctgaggctg ttcgacttca acaaacaggc tatccagaga 6360 ctgaaggcag aagcccagat gtcaatccag ctgatcaaca aggcagtgaa cgccctgatc 6420 aacgaccagc tgatcatgaa gaaccacctg agagacatta tgggcatccc ctactgtaat 6480 tacagcaagt attggtacct gaaccacact acaaccggga gaacatccct gcccaagtgc 6540 tggctggtca gcaatgggag ttatctgaat gaaacccatt tcagcgacga tatcgaacag 6600 caggctgaca acatgatcac agagatgctg cagaaagagt acatggaaag acagggcaag 6660 acaccactgg gactggtcga tctgttcgtc ttctccacta gcttctatct gatttccatc 6720 ttcctgcacc tggtgaagat ccccactcat aggcacattg tcggcaagag ttgccctaaa 6780 ccccataggc tgaatcacat ggggatttgt agttgcggcc tgtataagca gcctggcgtg 6840 cctgtgaagt ggaagagatg agcgcgcagc gcttagacgt ctcgcgatcg atactagtac 6900 aacctaaatc cattataaaa aacttaggag caaagtgatt gcctcccaag gtccacaatg 6960 acagagacct acgacttcga caagtcggca tgggacatca aagggtcgat cgctccgata 7020 caacccacca cctacagtga tggcaggctg gtgccccagg tcagagtcat agatcctggt 7080 ctaggcgaca ggaaggatga atgctttatg tacatgtttc tgctgggggt tgttgaggac 7140 agcgattccc tagggcctcc aatcgggcga gcatttgggt tcctgccctt aggtgttggc 7200 agatccacag caaagcccga aaaactcctc aaagaggcca ctgagcttga catagttgtt 7260 agacgtacag cagggctcaa tgaaaaactg gtgttctaca acaacacccc actaactctc 7320 ctcacacctt ggagaaaggt cctaacaaca gggagtgtct tcaacgcaaa ccaagtgtgc 7380 aatgcggtta atctgatacc gctcgatacc ccgcagaggt tccgtgttgt ttatatgagc 7440 atcacccgtc tttcggataa cgggtattac accgttccta gaagaatgct ggaattcaga 7500 tcggtcaatg cagtggcctt caacctgctg gtgaccctta ggattgacaa ggcgataggc 7560 cctgggaaga tcatcgacaa tacagagcaa cttcctgagg caacatttat ggtccacatc 7620 gggaacttca ggagaaagaa gagtgaagtc tactctgccg attattgcaa aatgaaaatc 7680 gaaaagatgg gcctggtttt tgcacttggt gggatagggg gcaccagtct tcacattaga 7740 agcacaggca aaatgagcaa gactctccat gcacaactcg ggttcaagaa gaccttatgt 7800 tacccgctga tggatatcaa tgaagacctt aatcgattac tctggaggag cagatgcaag 7860 atagtaagaa tccaggcagt tttgcagcca tcagttcctc aagaattccg catttacgac 7920 gacgtgatca taaatgatga ccaaggacta ttcaaagttc tgtagaccgt agtgcccagc 7980 aatgcccgaa aacgaccccc ctcacaatga cagccagaag gcccggacaa aaaagccccc 8040 tccgaaagac tccacggacc aagcgagagg ccagccagca gccgacggca agcgcgaaca 8100 ccaggcggcc ccagcacaga acagccctga cacaaggcca ccaccagcca ccccaatctg 8160 catcctcctc gtgggacccc cgaggaccaa cccccaaggc tgcccccgat ccaaaccacc 8220 aaccgcatcc ccaccacccc cgggaaagaa acccccagca attggaaggc ccctccccct 8280 cttcctcaac acaagaactc cacaaccgaa ccgcacaagc gaccgaggtg acccaaccgc 8340 aggcatccga ctccctagac agatcctctc tccccggcaa actaaacaaa acttagggcc 8400 aaggaacata cacacccaac agaacccaga ccccggccca cggcgccgcg cccccaaccc 8460 ccgacaacca gagggagccc ccaaccaatc ccgccggctc ccccggtgcc cacaggcagg 8520 gacaccaacc cccgaacaga cccagcaccc aaccatcgac aatccaagac gggggggccc 8580 ccccaaaaaa aggcccccag gggccgacag ccagcaccgc gaggaagccc acccacccca 8640 cacacgacca cggcaaccaa accagaaccc agaccaccct gggccaccag ctcccagact 8700 cggccatcac cccgcagaaa ggaaaggcca caacccgcgc accccagccc cgatccggcg 8760 gggagccacc caacccgaac cagcacccaa gagcgatccc cgaaggaccc ccgaaccgca 8820 aaggacatca gtatcccaca gcctctccaa gtcccccggt ctcctcctct tctcgaaggg 8880 accaaaagat caatccacca cacccgacga cactcaactc cccaccccta aaggagacac 8940 cgggaatccc agaatcaaga ctcatccaat gtccatcatg ggtctcaagg tgaacgtctc 9000 tgccatattc atggcagtac tgttaactct ccaaacaccc accggtcaaa tccattgggg 9060 caatctctct aagatagggg tggtaggaat aggaagtgca agctacaaag ttatgactcg 9120 ttccagccat caatcattag tcataaaatt aatgcccaat ataactctcc tcaataactg 9180 cacgagggta gagattgcag aatacaggag actactgaga acagttttgg aaccaattag 9240 agatgcactt aatgcaatga cccagaatat aagaccggtt cagagtgtag cttcaagtag 9300 gagacacaag agatttgcgg gagtagtcct ggcaggtgcg gccctaggcg ttgccacagc 9360 tgctcagata acagccggca ttgcacttca ccagtccatg ctgaactctc aagccatcga 9420 caatctgaga gcgagcctgg aaactactaa tcaggcaatt gagacaatca gacaagcagg 9480 gcaggagatg atattggctg ttcagggtgt ccaagactac atcaataatg agctgatacc 9540 gtctatgaac caactatctt gtgatttaat cggccagaag ctcgggctca aattgctcag 9600 atactataca gaaatcctgt cattatttgg ccccagttta cgggacccca tatctgcgga 9660 gatatctatc caggctttga gctatgcgct tggaggagac atcaataagg tgttagaaaa 9720 gctcggatac agtggaggtg atttactggg catcttagag agcggaggaa taaaggcccg 9780 gataactcac gtcgacacag agtcctactt cattgtcctc agtatagcct atccgacgct 9840 gtccgagatt aagggggtga ttgtccaccg gctagagggg gtctcgtaca acataggctc 9900 tcaagagtgg tataccactg tgcccaagta tgttgcaacc caagggtacc ttatctcgaa 9960 ttttgatgag tcatcgtgta ctttcatgcc agaggggact gtgtgcagcc aaaatgcctt 10020 gtacccgatg agtcctctgc tccaagaatg cctccggggg tacaccaagt cctgtgctcg 10080 tacactcgta tccgggtctt ttgggaaccg gttcatttta tcacaaggga acctaatagc 10140 caattgtgca tcaatccttt gcaagtgtta cacaacagga acgatcatta atcaagaccc 10200 tgacaagatc ctaacataca ttgctgccga tcactgcccg gtagtcgagg tgaacggcgt 10260 gaccatccaa gtcgggagca ggaggtatcc agacgctgtg tacttgcaca gaattgacct 10320 cggtcctccc atatcattgg agaggttgga cgtagggaca aatctgggga atgcaattgc 10380 taagttggag gatgccaagg aattgttgga gtcatcggac cagatattga ggagtatgaa 10440 aggtttatcg agcactagca tagtctacat cctgattgca gtgtgtcttg gagggttgat 10500 agggatcccc gctttaatat gttgctgcag ggggcgttgt aacaaaaagg gagaacaagt 10560 tggtatgtca agaccaggcc taaagcctga tcttacggga acatcaaaat cctatgtaag 10620 gtcgctctga tcctctacaa ctcttgaaac acaaatgtcc cacaagtctc ctcttcgtca 10680 tcaagcaacc accgcaccca gcatcaagcc cacctgaaat tatctccggc ttccctctgg 10740 ccgaacaata tcggtagtta atcaaaactt agggtgcaag atcatccaca atgtcaccac 10800 aacgagaccg gataaatgcc ttctacaaag ataaccccca tcccaaggga agtaggatag 10860 tcattaacag agaacatctt atgattgata gaccttatgt tttgctggct gttctgtttg 10920 tcatgtttct gagcttgatc gggttgctag ccattgcagg cattagactt catcgggcag 10980 ccatctacac cgcagagatc cataaaagcc tcagcaccaa tctagatgta actaactcaa 11040 tcgagcatca ggtcaaggac gtgctgacac cactcttcaa aatcatcggt gatgaagtgg 11100 gcctgaggac acctcagaga ttcactgacc tagtgaaatt aatctctgac aagattaaat 11160 tccttaatcc ggatagggag tacgacttca gagatctcac ttggtgtatc aacccgccag 11220 agagaatcaa attggattat gatcaatact gtgcagatgt ggctgctgaa gagctcatga 11280 atgcattggt gaactcaact ctactggaga ccagaacaac caatcagttc ctagctgtct 11340 caaagggaaa ctgctcaggg cccactacaa tcagaggtca attctcaaac atgtcgctgt 11400 ccctgttaga cttgtattta ggtcgaggtt acaatgtgtc atctatagtc actatgacat 11460 cccagggaat gtatggggga acttacctag tggaaaagcc taatctgagc agcaaaaggt 11520 cagagttgtc acaactgagc atgtaccgag tgtttgaagt aggtgttatc agaaatccgg 11580 gtttgggggc tccggtgttc catatgacaa actatcttga gcaaccagtc agtaatgatc 11640 tcagcaactg tatggtggct ttgggggagc tcaaactcgc agccctttgt cacggggaag 11700 attctatcac aattccctat cagggatcag ggaaaggtgt cagcttccag ctcgtcaagc 11760 taggtgtctg gaaatcccca accgacatgc aatcctgggt ccccttatca acggatgatc 11820 cagtgataga caggctttac ctctcatctc acagaggtgt tatcgctgac aatcaagcaa 11880 aatgggctgt cccgacaaca cgaacagatg acaagttgcg aatggagaca tgcttccaac 11940 aggcgtgtaa gggtaaaatc caagcactct gcgagaatcc cgagtgggca ccattgaagg 12000 ataacaggat tccttcatac ggggtcttgt ctgttgatct gagtctgaca gttgagctta 12060 aaatcaaaat tgcttcggga ttcgggccat tgatcacaca cggttcaggg atggacctat 12120 acaaatccaa ccacaacaat gtgtattggc tgactatccc gccaatgaag aacctagcct 12180 taggtgtaat caacacattg gagtggatac cgagattcaa ggttagtccc tacctcttca 12240 ctgtcccaat taaggaagca ggcgaagact gccatgcccc aacataccta cctgcggagg 12300 tggatggtga tgtcaaactc agttccaatc tggtgattct acctggtcaa gatctccaat 12360 atgttttggc aacctacgat acttccaggg ttgaacatgc tgtggtttat tacgtttaca 12420 gcccaagccg ctcattttct tacttttatc cttttaggtt gcctataaag ggggtcccca 12480 tcgaattaca agtggaatgc ttcacatggg accaaaaact ctggtgccgt cacttctgtg 12540 tgcttgcgga ctcagaatct ggtggacata tcactcactc tgggatggtg ggcatgggag 12600 tcagctgcac agtcacccgg gaagatggaa ccaatcgcag atagggctgc tagtgaacca 12660 atcacatgat gtcacccaga catcaggcat acccactagt gtgaaataga catcagaatt 12720 aagaaaaacg tagggtccaa gtggttcccc gttatggact cgctatctgt caaccagatc 12780 ttataccctg aagttcacct agatagcccg atagttacca ataagatagt agccatcctg 12840 gagtatgctc gagtccctca cgcttacagc ctggaggacc ctacactgtg tcagaacatc 12900 aagcaccgcc taaaaaacgg attttccaac caaatgatta taaacaatgt ggaagttggg 12960 aatgtcatca agtccaagct taggagttat ccggcccact ctcatattcc atatccaaat 13020 tgtaatcagg atttatttaa catagaagac aaagagtcaa cgaggaagat ccgtgaactc 13080 ctcaaaaagg ggaattcgct gtactccaaa gtcagtgata aggttttcca atgcttaagg 13140 gacactaact cacggcttgg cctaggctcc gaattgaggg aggacatcaa ggagaaagtt 13200 attaacttgg gagtttacat gcacagctcc cagtggtttg agccctttct gttttggttt 13260 acagtcaaga ctgagatgag gtcagtgatt aaatcacaaa cccatacttg ccataggagg 13320 agacacacac ctgtattctt cactggtagt tcagttgagt tgctaatctc tcgtgacctt 13380 gttgctataa tcagtaaaga gtctcaacat gtatattacc tgacatttga actggttttg 13440 gttgctataa tcagtaaaga gtctcaacat gtatattacc tgacatttga actggttttg 13440 atgtattgtg atgtcataga ggggaggtta atgacagaga ccgctatgac tattgatgct 13500 atgtattgtg atgtcataga ggggaggtta atgacagaga ccgctatgac tattgatgct 13500 aggtatacag agcttctagg aagagtcaga tacatgtgga aactgataga tggtttcttc 13560 aggtatacag agcttctagg aagagtcaga tacatgtgga aactgataga tggtttcttc 13560 cctgcactcg ggaatccaac ttatcaaatt gtagccatgc tggagcctct ttcacttgct 13620 cctgcactcg ggaatccaac ttatcaaatt gtagccatgc tggagcctct ttcacttgct 13620 tacctgcagc tgagggatat aacagtagaa ctcagaggtg ctttccttaa ccactgcttt 13680 tacctgcagc tgagggatat aacagtagaa ctcagaggtg ctttccttaa ccactgcttt 13680 actgaaatac atgatgttct tgaccaaaac gggttttctg atgaaggtac ttatcatgag 13740 actgaaatac atgatgttct tgaccaaaac gggttttctg atgaaggtac ttatcatgag 13740 ttaactgaag ctctagatta cattttcata actgatgaca tacatctgac aggggagatt 13800 ttaactgaag ctctagatta cattttcata actgatgaca tacatctgac aggggagatt 13800 ttctcatttt tcagaagttt cggccacccc agacttgaag cagtaacggc tgctgaaaat 13860 ttctcatttt tcagaagttt cggccacccc agacttgaag cagtaacggc tgctgaaaat 13860 gttaggaaat acatgaatca gcctaaagtc attgtgtatg agactctgat gaaaggtcat 13920 gttaggaaat acatgaatca gcctaaagtc attgtgtatg agactctgat gaaaggtcat 13920 gccatatttt gtggaatcat aatcaacggc tatcgtgaca ggcacggagg cagttggcca 13980 gccatatttt gtggaatcat aatcaacggc tatcgtgaca ggcacggagg cagttggcca 13980 ccgctgaccc tccccctgca tgctgcagac acaatccgga atgctcaagc ttcaggtgaa 14040 ccgctgaccc tccccctgca tgctgcagac acaatccgga atgctcaagc ttcaggtgaa 14040 gggttaacac atgagcagtg cgttgataac tggaaatctt ttgctggagt gaaatttggc 14100 tgctttatgc ctcttagcct ggatagtgat ctgacaatgt acctaaagga caaggcactt 14160 gctgctctcc aaagggaatg ggattcagtt tacccgaaag agttcctgcg ttacgaccct 14220 cccaagggaa ccgggtcacg gaggcttgta gatgttttcc ttaatgattc gagctttgac 14280 ccatatgatg tgataatgta tgttgtaagt ggagcttacc tccatgaccc tgagttcaac 14340 ctgtcttaca gcctgaaaga aaaggagatc aaggaaacag gtagactttt tgctaaaatg 14400 acttacaaaa tgagggcatg ccaagtgatt gctgaaaatc taatctcaaa cgggattggc 14460 aaatatttta aggacaatgg gatggccaag gatgagcacg atttgactaa ggcactccac 14520 actctagctg tctcaggagt ccccaaagat ctcaaagaaa gtcacagggg ggggccagtc 14580 ttaaaaacct actcccgaag cccagtccac acaagtacca ggaacgtgag agcagcaaaa 14640 gggtttatag ggttccctca agtaattcgg caggaccaag acactgatca tccggagaat 14700 atggaagctt acgagacagt cagtgcattt atcacgactg atctcaagaa gtactgcctt 14760 aattggagat atgagaccat cagcttgttt gcacagaggc taaatgagat ttacggattg 14820 ccctcatttt tccagtggct gcataagagg cttgagacct ctgtcctgta tgtaagtgac 14880 cctcattgcc cccccgacct tgacgcccat atcccgttat ataaagtccc caatgatcaa 14940 atcttcatta agtaccctat gggaggtata gaagggtatt gtcagaagct gtggaccatc 15000 agcaccattc cctatctata cctggctgct tatgagagcg gagtaaggat tgcttcgtta 15060 gtgcaagggg acaatcagac catagccgta acaaaaaggg tacccagcac atggccctac 15120 aaccttaaga aacgggaagc tgctagagta actagagatt actttgtaat tcttaggcaa 15180 aggctacatg atattggcca tcacctcaag gcaaatgaga caattgtttc atcacatttt 15240 tttgtctatt caaaaggaat atattatgat gggctacttg tgtcccaatc actcaagagc 15300 atcgcaagat gtgtattctg gtcagagact atagttgatg aaacaagggc agcatgcagt 15360 aatattgcta caacaatggc taaaagcatc gagagaggtt atgaccgtta ccttgcatat 15420 tccctgaacg tcctaaaagt gatacagcaa attctgatct ctcttggctt cacaatcaat 15480 tcaaccatga cccgggatgt agtcataccc ctcctcacaa acaacgacct cttaataagg 15540 atggcactgt tgcccgctcc tattgggggg atgaattatc tgaatatgag caggctgttt 15600 gtcagaaaca tcggtgatcc agtaacatca tcaattgctg atctcaagag aatgattctc 15660 gcctcactaa tgcctgaaga gaccctccat caagtaatga cacaacaacc gggggactct 15720 tcattcctag actgggctag cgacccttac tcagcaaatc ttgtatgtgt ccagagcatc 15780 actagactcc tcaagaacat aactgcaagg tttgtcctga tccatagtcc aaacccaatg 15840 ttaaaaggat tattccatga tgacagtaaa gaagaggacg agggactggc ggcattcctc 15900 atggacaggc atattatagt acctagggca gctcatgaaa tcctggatca tagtgtcaca 15960 ggggcaagag agtctattgc aggcatgctg gataccacaa aaggcttgat tcgagccagc 16020 atgaggaagg gggggttaac ctctcgagtg ataaccagat tgtccaatta tgactatgaa 16080 caattcagag cagggatggt gctattgaca ggaagaaaga gaaatgtcct cattgacaaa 16140 gagtcatgtt cagtgcagct ggcgagagct ctaagaagcc atatgtgggc gaggctagct 16200 gagtcatgtt cagtgcagct ggcgagagct ctaagaagcc atatgtgggc gaggctagct 16200 cgaggacggc ctatttacgg ccttgaggtc cctgatgtac tagaatctat gcgaggccac 16260 cgaggacggc ctatttacgg ccttgaggtc cctgatgtac tagaatctat gcgaggccac 16260 cttattcggc gtcatgagac atgtgtcatc tgcgagtgtg gatcagtcaa ctacggatgg 16320 cttattcggc gtcatgagac atgtgtcatc tgcgagtgtg gatcagtcaa ctacggatgg 16320 ttttttgtcc cctcgggttg ccaactggat gatattgaca aggaaacatc atccttgaga 16380 ttttttgtcc cctcgggttg ccaactggat gatattgaca aggaaacatc atccttgaga 16380 gtcccatata ttggttctac cactgatgag agaacagaca tgaagcttgc cttcgtaaga 16440 gtcccatata ttggttctac cactgatgag agaacagaca tgaagcttgc cttcgtaaga 16440 gccccaagtc gatccttgcg atctgctgtt agaatagcaa cagtgtactc atgggcttac 16500 gccccaagtc gatccttgcg atctgctgtt agaatagcaa cagtgtactc atgggcttac 16500 ggtgatgatg atagctcttg gaacgaagcc tggttgttgg ctaggcaaag ggccaatgtg 16560 ggtgatgatg atagctcttg gaacgaagcc tggttgttgg ctaggcaaag ggccaatgtg 16560 agcctggagg agctaagggt gatcactccc atctcaactt cgactaattt agcgcatagg 16620 agcctggagg agctaagggt gatcactccc atctcaactt cgactaattt agcgcatagg 16620 ttgagggatc gtagcactca agtgaaatac tcaggtacat cccttgtccg agtggcgagg 16680 ttgagggatc gtagcactca agtgaaatac tcaggtacat cccttgtccg agtggcgagg 16680 tataccacaa tctccaacga caatctctca tttgtcatat cagataagaa ggttgatact 16740 tataccacaa tctccaacga caatctctca tttgtcatat cagataagaa ggttgatact 16740 aactttatat accaacaagg aatgcttcta gggttgggtg ttttagaaac attgtttcga 16800 aactttatat accaacaagg aatgcttcta gggttgggtg ttttagaaac attgtttcga 16800 ctcgagaaag ataccggatc atctaacacg gtattacatc ttcacgtcga aacagattgt 16860 tgcgtgatcc cgatgataga tcatcccagg atacccagct cccgcaagct agagctgagg 16920 gcagagctat gtaccaaccc attgatatat gataatgcac ctttaattga cagagatgca 16980 acaaggctat acacccagag ccataggagg caccttgtgg aatttgttac atggtccaca 17040 ccccaactat atcacatttt agctaagtcc acagcactat ctatgattga cctggtaaca 17100 aaatttgaga aggaccatat gaatgaaatt tcagctctca taggggatga cgatatcaat 17160 agtttcataa ctgagtttct gctcatagag ccaagattat tcactatcta cttgggccag 17220 tgtgcggcca tcaattgggc atttgatgta cattatcata gaccatcagg gaaatatcag 17280 atgggtgagc tgttgtcatc gttcctttct agaatgagca aaggagtgtt taaggtgctt 17340 gtcaatgctc taagccaccc aaagatctac aagaaattct ggcattgtgg tattatagag 17400 cctatccatg gtccttcact tgatgctcaa aacttgcaca caactgtgtg caacatggtt 17460 tacacatgct atatgaccta cctcgacctg ttgttgaatg aagagttaga agagttcaca 17520 tttctcttgt gtgaaagcga cgaggatgta gtaccggaca gattcgacaa catccaggca 17580 aaacacttat gtgttctggc agatttgtac tgtcaaccag ggacctgccc accaattcga 17640 ggtctaagac cggtagagaa atgtgcagtt ctaaccgacc atatcaaggc agaggctatg 17700 ttatctccag caggatcttc gtggaacata aatccaatta ttgtagacca ttactcatgc 17760 tctctgactt atctccggcg aggatcgatc aaacagataa gattgagagt tgatccagga 17820 ttcattttcg acgccctcgc tgaggtaaat gtcagtcagc caaagatcgg cagcaacaac 17880 atctcaaata tgagcatcaa ggctttcaga cccccacacg atgatgttgc aaaattgctc 17940 aaagatatca acacaagcaa gcacaatctt cccatttcag ggggcaatct cgccaattat 18000 gaaatccatg ctttccgcag aatcgggttg aactcatctg cttgctacaa agctgttgag 18060 atatcaacat taattaggag atgccttgag ccaggggagg acggcttgtt cttgggtgag 18120 ggatcgggtt ctatgttgat cacttataaa gagatactta aactaaacaa gtgcttctat 18180 aatagtgggg tttccgccaa ttctagatct ggtcaaaggg aattagcacc ctatccctcc 18240 gaagttggcc ttgtcgaaca cagaatggga gtaggtaata ttgtcaaagt gctctttaac 18300 gggaggcccg aagtcacgtg ggtaggcagt gtagattgct tcaatttcat agttagtaat 18360 atccctacct ctagtgtggg gtttatccat tcagatatag agaccttgcc tgacaaagat 18420 actatagaga agctagagga attggcagcc atcttatcga tggctctgct cctgggcaaa 18480 ataggatcaa tactggtgat taagcttatg cctttcagcg gggattttgt tcagggattt 18540 ataagttatg tagggtctca ttatagagaa gtgaaccttg tataccctag atacagcaac 18600 ttcatctcta ctgaatctta tttggttatg acagatctca aggctaaccg gctaatgaat 18660 cctgaaaaga ttaagcagca gataattgaa tcatctgtga ggacttcacc tggacttata 18720 ggtcacatcc tatccattaa gcaactaagc tgcatacaag caattgtggg agacgcagtt 18780 agtagaggtg atatcaatcc tactctgaaa aaacttacac ctatagagca ggtgctgatc 18840 aattgcgggt tggcaattaa cggacctaag ctgtgcaaag aattgatcca ccatgatgtt 18900 gcctcagggc aagatggatt gcttaattct atactcatcc tctacaggga gttggcaaga 18960 gcctcagggc aagatggatt gcttaattct atactcatcc tctacaggga gttggcaaga 18960 ttcaaagaca accaaagaag tcaacaaggg atgttccacg cttaccccgt attggtaagt 19020 ttcaaagaca accaaagaag tcaacaaggg atgttccacg cttaccccgt attggtaagt 19020 agcaggcaac gagaacttat atctaggatc acccgcaaat tctgggggca cattcttctt 19080 agcaggcaac gagaacttat atctaggatc acccgcaaat tctgggggca cattcttctt 19080 tactccggga acaaaaagtt gataaataag tttatccaga atctcaagtc cggctatctg 19140 tactccggga acaaaaagtt gataaataag tttatccaga atctcaagtc cggctatctg 19140 atactagact tacaccagaa tatcttcgtt aagaatctat ccaagtcaga gaaacagatt 19200 atactagact tacaccagaa tatcttcgtt aagaatctat ccaagtcaga gaaacagatt 19200 attatgacgg ggggtttgaa acgtgagtgg gtttttaagg taacagtcaa ggagaccaaa 19260 attatgacgg ggggtttgaa acgtgagtgg gtttttaagg taacagtcaa ggagaccaaa 19260 gaatggtata agttagtcgg atacagtgcc ctgattaagg actaattggt tgaactccgg 19320 gaatggtata agttagtcgg atacagtgcc ctgattaagg actaattggt tgaactccgg 19320 aaccctaatc ctgccctagg tggttaggca ttatttgcaa tatattaaag aaaactttga 19380 aaccctaatc ctgccctagg tggttaggca ttatttgcaa tatattaaag aaaactttga 19380 aaatacgaag tttctattcc cagctttgtc tggtggccgg catggtccca gcctcctcgc 19440 aaatacgaag tttctattcc cagctttgtc tggtggccgg catggtccca gcctcctcgc 19440 tggcgccggc tgggcaacat tccgagggga ccgtcccctc ggtaatggcg aatgggacgc 19500 tggcgccggc tgggcaacat tccgagggga ccgtcccctc ggtaatggcg aatgggacgc 19500 ggccgatccg gctgctaaca aagcccgaaa ggaagctgag ttggctgctg ccaccgctga 19560 ggccgatccg gctgctaaca aagcccgaaa ggaagctgag ttggctgctg ccaccgctga 19560 gcaataacta gcataacccc ttggggcctc taaacgggtc ttgaggggtt ttttgctgaa 19620 aggaggaact atatccggat gcggccgcgg gccctatggt acccagcttt tgttcccttt 19680 agtgagggtt aattccgagc ttggcgtaat catggtcata gctgtttcct gtgtgaaatt 19740 gttatccgct cacaattcca cacaacatag gagccggaag cataaagtgt aaagcctggg 19800 gtgcctaatg agtgaggtaa ctcacattaa ttgcgttgcg ctcactgccc gctttccagt 19860 cgggaaacct gtcgtgccag ctgcattaat gaatcggcca acgcgcgggg agaggcggtt 19920 tgcgtattgg gcgctcttcc gcttcctcgc tcactgactc gctgcgctcg gtcgttcggc 19980 tgcggcgagc ggtatcagct cactcaaagg cggtaatacg gttatccaca gaatcagggg 20040 ataacgcagg aaagaacatg tgagcaaaag gccagcaaaa ggccaggaac cgtaaaaagg 20100 ccgcgttgct ggcgtttttc cataggctcg gcccccctga cgagcatcac aaaaatcgac 20160 gctcaagtca gaggtggcga aacccgacag gactataaag ataccaggcg ttcccccctg 20220 gaagctccct cgtgcgctct cctgttccga ccctgccgct taccggatac ctgtccgcct 20280 ttctcccttc gggaagcgtg gcgctttctc aatgctcacg ctgtaggtat ctcagttcgg 20340 tgtaggtcgt tcgctccaag ctgggctgtg tgcacgaacc ccccgttcag cccgaccgct 20400 gcgccttatc cggtaactat cgtcttgagt ccaacccggt aagacacgac ttatcgccac 20460 tggcagcagc cactggtaac aggattagca gagcgaggta tgtaggcggt gctacagagt 20520 tcttgaagtg gtggcctaac tacggctaca ctagaaggac agtatttggt atctgcgctc 20580 tgctgaagcc agttaccttc ggaaaaagag ttggtagctc ttgatccggc aaacaaacca 20640 ccgctggtag cggtggtttt tttgtttgca agcagcagat tacgcgcaga aaaaaaggat 20700 ctcaagaaga tcctttgatc ttttctacgg ggtctgacgc tcagtggaac gaaaactcac 20760 gttaagggat tttggtcatg agattatcaa aaaggatctt cacctagatc cttttaaatt 20820 aaaaatgaag ttttaaatca atctaaagta tatatgagta aacttggtct gacagttacc 20880 aatgcttaat cagtgaggca cctatctcag cgatctgtct atttcgttca tccatagttg 20940 cctgactgcc cgtcgtgtag ataactacga tacgggaggg cttaccatct ggccccagtg 21000 ctgcaatgat accgcgagac ccacgctcac cggctccaga tttatcagca ataaaccagc 21060 cagccggaag ggccgagcgc agaagtggtc ctgcaacttt atccgcctcc atccagtcta 21120 ttaattgttg ccgggaagct agagtaagta gttcgccagt taatagtttg cgcaacgttg 21180 ttgccattgc tacaggcatc gtggtgtcac gctcgtcgtt tggtatggct tcattcagct 21240 ccggttccca acgatcaagg cgagttacat gatcccccat gttgtgaaaa aaagcggtta 21300 gctccttcgg tcctccgatc gttgtcagaa gtaagttggc cgcagtgtta tcactcatgc 21360 ttatggcagc actgcataat tctcttactg tcatgccatc cgtaagatgc ttttctgtga 21420 ctggtgagta ctcaaccaag tcattctgag aatagtgtat gcggcgaccg agttgctctt 21480 gcccggcgtc aatacgggat aataccgcgc cacatagcag aactttaaaa gtgctcatca 21540 ttggaaaacg ttcttcgggg cgaaaactct caaggatctt accgctgttg agatccagtt 21600 cgatgtaacc cactcgtgca cccaactgat cttcagcatc ttttactttc accagcgttt 21660 ctgggtgagc aaaaacagga aggcaaaatg ccgcaaaaaa gggaataagg gcgacacgga 21720 aatgttgaat actcatactc ttcctttttc aatattattg aagcatttat cagggttatt 21780 gtctcatgag cggatacata tttgaatgta tttagaaaaa taaacaaata ggggttccgc 21840 gcacatttcc ccgaaaagtg ccacctgaaa ttgtaaacgt taatattttg ttaaaattcg 21900 cgttaaattt ttgttaaatc agctcatttt ttaaccaata ggccgaaatc ggcaaaatcc 21960 cttataaatc aaaagaatag accgagatag ggttgagtgt tgttccagtt tggaacaaga 22020 gtccactatt aaagaacgtg gactccaacg tcaaagggcg aaaaaccgtc tatcagggcg 22080 atggcccact acgtgaacca tcaccctaat caagtttttt ggggtcgagg tgccgtaaag 22140 cactaaatcg gaaccctaaa gggagccccc gatttagagc ttgacgggga aagccggcga 22200 acgtggcgag aaaggaaggg aagaaagcga aaggagcggg cgctagggcg ctggcaagtg 22260 tagcggtcac gctgcgcgta accaccacac ccgccgcgct taatgcgccg ctacagggcg 22320 cgtcccattc gccattcagg ctgcgcaact gttgggaagg gcgatcggtg cgggcctctt 22380 cgctattacg ccagccaccg cggtg 22405 <210> 11 <211> 22405 <212> DNA <213> Artificial Sequence <220> <223> Plasmid MeV-mNP+GPC <400> 11 gcggccgcta atacgactca ctatagggcc aactttgttt ggtctgatga gtccgtgagg 60 acgaaacccg gagtcccggg tcaccaaaca aagttgggta aggatagttc aatcaatgat 120 catcttctag tgcacttagg attcaagatc ctattatcag ggacaagagc aggattaggg 180 atatccgaga tggccacact tttaaggagc ttagcattgt tcaaaagaaa caaggacaaa 240 ccacccatta catcaggatc cggtggagcc atcagaggaa tcaaacacat tattatagta 300 ccaatccctg gagattcctc aattaccact cgatccagac ttctggaccg gttggtgagg 360 ttaattggaa acccggatgt gagcgggccc aaactaacag gggcactaat aggtatatta 420 tccttatttg tggagtctcc aggtcaattg attcagagga tcaccgatga ccctgacgtt 480 agcataaggc tgttagaggt tgtccagagt gaccagtcac aatctggcct taccttcgca 540 tcaagaggta ccaacatgga ggatgaggcg gaccaatact tttcacatga tgatccaatt 600 agtagtgatc aatccaggtt cggatggttc gggaacaagg aaatctcaga tattgaagtg 660 caagaccctg agggattcaa catgattctg ggtaccatcc tagcccaaat ttgggtcttg 720 ctcgcaaagg cggttacggc cccagacacg gcagctgatt cggagctaag aaggtggata 780 aagtacaccc aacaaagaag ggtagttggt gaatttagat tggagagaaa atggttggat 840 gtggtgagga acaggattgc cgaggacctc tccttacgcc gattcatggt cgctctaatc 900 ctggatatca agagaacacc cggaaacaaa cccaggattg ctgaaatgat atgtgacatt 960 gatacatata tcgtagaggc aggattagcc agttttatcc tgactattaa gtttgggata 1020 gaaactatgt atcctgctct tggactgcat gaatttgctg gtgagttatc cacacttgag 1080 tccttgatga acctttacca gcaaatgggg gaaactgcac cctacatggt aatcctggag 1140 aactcaattc agaacaagtt cagtgcagga tcataccctc tgctctggag ctatgccatg 1200 ggagtaggag tggaacttga aaactccatg ggaggtttga actttggccg atcttacttt 1260 gatccagcat attttagatt agggcaagag atggtaagga ggtcagctgg aaaggtcagt 1320 tccacattgg catctgaact cggtatcact gccgaggatg caaggcttgt ttcagagatt 1380 gcaatgcata ctactgagga caagatcagt agagcggttg gacccagaca agcccaagta 1440 tcatttctac acggtgatca aagtgagaat gagctaccga gattgggggg caaggaagat 1500 aggagggtca aacagagtcg aggagaagcc agggagagct acagagaaac cgggcccagc 1560 agagcaagtg atgcgagagc tgcccatctt ccaaccggca cacccctaga cattgacact 1620 gcaacggagt ccagccaaga tccgcaggac agtcgaaggt cagctgacgc cctgcttagg 1680 ctgcaagcca tggcaggaat ctcggaagaa caaggctcag acacggacac ccctatagtg 1740 tacaatgaca gaaatcttct agactaggtg cgagaggccg agggccagaa caacatccgc 1800 ctaccatcca tcattgttat aaaaaactta ggaaccaggt ccacacagcc gccagcccat 1860 caaccatcca ctcccacgat tggagccaat ggcagaagag caggcacgcc atgtcaaaaa 1920 cggactggaa tgcatccggg ctctcaaggc cgagcccatc ggctcactgg ccatcgagga 1980 agctatggca gcatggtcag aaatatcaga caacccagga caggagcgag ccacctgcag 2040 ggaagagaag gcaggcagtt cgggtctcag caaaccatgc ctctcagcaa ttggatcaac 2100 tgaaggcggt gcacctcgca tccgcggtca gggacctgga gagagcgatg acgacgctga 2160 aactttggga atccccccaa gaaatctcca ggcatcaagc actgggttac agtgttatta 2220 cgtttatgat cacagcggtg aagcggttaa gggaatccaa gatgctgact ctatcatggt 2280 tcaatcaggc cttgatggtg atagcaccct ctcaggagga gacaatgaat ctgaaaacag 2340 cgatgtggat attggcgaac ctgataccga gggatatgct atcactgacc ggggatctgc 2400 tcccatctct atggggttca gggcttctga tgttgaaact gcagaaggag gggagatcca 2460 cgagctcctg agactccaat ccagaggcaa caactttccg aagcttggga aaactctcaa 2520 tgttcctccg cccccggacc ccggtagggc cagcacttcc gggacaccca ttaaaaaggg 2580 cacagacgcg agattagcct catttggaac ggagatcgcg tctttattga caggtggtgc 2640 aacccaatgt gctcgaaagt caccctcgga accatcaggg ccaggtgcac ctgcggggaa 2700 tgtccccgag tgtgtgagca atgccgcact gatacaggag tggacacccg aatctggtac 2760 cacaatctcc ccgagatccc agaataatga agaaggggga gactattatg atgatgagct 2820 gttctctgat gtccaagata ttaaaacagc cttggccaaa atacacgagg ataatcagaa 2880 gataatctcc aagctagaat cactgctgtt attgaaggga gaagttgagt caattaagaa 2940 gcagatcaac aggcaaaata tcagcatatc caccctggaa ggacacctct caagcatcat 3000 gatcgccatt cctggacttg ggaaggatcc caacgacccc actgcagatg tcgaaatcaa 3060 tcccgacttg aaacccatca taggcagaga ttcaggccga gcactggccg aagttctcaa 3120 gaaacccgtt gccagccgac aactccaagg aatgacaaat ggacggacca gttccagagg 3180 acagctgctg aaggaatttc agctaaagcc gatcgggaaa aagatgagct cagccgtcgg 3240 gtttgttcct gacaccggcc ctgcatcacg cagtgtaatc cgctccatta taaaatccag 3300 ccggctagag gaggatcgga agcgttacct gatgactctc cttgatgata tcaaaggagc 3360 caatgatctt gccaagttcc accagatgct gatgaagata ataatgaagt agctacagct 3420 caacttacct gccaacccca tgccagtcga cccaactagc ctaccctcca tcattgttat 3480 aaaaaactta ggaaccaggt ccacacagcc gccagcccat caacgcgtac gatgagtgcc 3540 agcaaagaaa tcaagagctt cctgtggacc cagagtctgc ggagggaact gagcggatac 3600 tgtagcaaca tcaaactgca ggtggtcaag gacgctcagg cactgctgca tgggctggac 3660 ttctccgagg tgtctaatgt gcagcggctg atgcggaaag aacggaggga cgataatgac 3720 ctgaagcgac tgcgcgacct gaaccaggca gtgaacaatc tggtcgagct gaagagcacc 3780 cagcagaaat caatcctgcg ggtcgggaca ctgacatctg acgacctgct gatcctggct 3840 gcagacctgg agaagctgaa atcgaaagtg atccgcaccg aaaggccact gtccgccggg 3900 gtctacatgg gcaatctgtc ttcccagcag ctggaccaga ggcgggctct gctgaacatg 3960 attgggatgt ccggaggaaa tcagggagct agagccggga gggacggagt cgtgcgggtc 4020 tgggacgtga agaatgccga actgctgaac aaccagttcg ggaccatgcc aagtctgaca 4080 ctggcatgcc tgactaaaca gggccaggtg gatctgaatg atgcagtcca ggctctgacc 4140 gacctgggcc tgatctacac cgccaagtac cccaatacta gcgacctgga tagactgacc 4200 cagagccacc ccatcctgaa catgatcgac actaagaagt cctcactgaa catcagtggc 4260 tataatttct ccctgggggc agcagtcaag gctggcgcat gcatgctgga cggcgggaat 4320 atgctggaaa ccatcaaagt gtctccccag accatggatg gcatcctgaa atctattctg 4380 aaagtcaaga aggccctggg aatgtttatt tcagacaccc ccggcgagag gaatccatat 4440 gagaacattc tgtataagat ttgcctgagt ggcgacgggt ggccatacat tgcaagccgg 4500 acatcaatta ccggaagagc ttgggagaat acagtcgtgg acctggaaag cgacggcaag 4560 ccccagaagg ccgactcaaa caactcctca aagagtctgc agtcagctgg cttcacagca 4620 gggctgactt actcccagct gatgacactg aaggacgcaa tgctgcagct ggacccaaac 4680 gctaagacat ggatggccat cgaggcccgg ccagaagatc cagtggaaat cgcactgtat 4740 cagccatcat ccggatgcta tatccatttc ttccgggaac caactgatct gaagcagttc 4800 aagcaggatg caaagtactc ccacggaatc gatgtcaccg atctgttcgc aacccagcca 4860 ggactgacat cagccgtcat cgatgccctg cctaggaaca tggtcattac ttgccagggc 4920 tccgacgata ttaggaagct gctggagagc cagggacgga aggatatcaa actgatcgat 4980 attgccctgt ctaagactga tagccggaaa tatgagaatg cagtctggga tcagtacaag 5040 gacctgtgcc atatgcatac cggagtggtc gtcgagaaga agaagagggg cggaaaggaa 5100 gagatcacac cccactgtgc cctgatggat tgcatcatgt tcgacgcagc cgtgtccggg 5160 ggcctgaaca cctcagtcct gagggctgtc ctgccaagag atatggtgtt tagaacttca 5220 accccaagag tcgtcctgta attcgaacta cagctcaact tacctgccaa ccccatgcca 5280 gtcgacccaa ctagtacaac ctaaatccat tataaaaaac ttaggaacca ggtccacaca 5340 gccgccagcc catcaaccat ccactcccac gattggaggc cggccatggg ccagattgtc 5400 acattctttc aggaagtgcc acacgtcatt gaggaggtca tgaacatcgt gctgattgct 5460 ctgtcagtgc tggcagtgct gaaaggactg tacaacttcg ctacctgtgg actggtggga 5520 ctggtcacat tcctgctgct gtgcggcaga agttgcacta cctcactgta caaaggagtg 5580 tacgagctgc agactctgga actgaacatg gagacactga atatgacaat gcctctgagc 5640 tgcaccaaga ataatagcca ccactatatc atggtcggga acgaaaccgg cctggaactg 5700 accctgacaa acaccagcat cattaaccac aagttctgca atctgagcga cgctcacaag 5760 aagaacctgt atgaccacgc tctgatgtcc atcatcagta cctttcacct gtccatcccc 5820 aatttcaacc agtacgaggc aatgtcatgc gacttcaacg ggggcaagat cagtgtccag 5880 tacaacctga gccactccta cgccggcgac gcagccaacc actgcggaac tgtcgccaat 5940 ggcgtgctgc agacattcat gaggatggca tgggggggat cttacatcgc actggatagc 6000 ggcaggggca attgggattg catcatgact tcctatcagt atctgattat ccagaatact 6060 acatgggagg atcattgcca gttcagtcgg cccagcccta ttggatatct ggggctgctg 6120 tcacagagaa cacgggatat ctatatttca agacgcctgc tgggcacatt cacttggaca 6180 ctgtcagaca gtgagggcaa ggatactcca gggggctact gcctgacacg atggatgctg 6240 atcgaagcag agctgaaatg cttcggcaat accgcagtgg ccaagtgcaa cgagaaacac 6300 gacgaggagt tctgcgacat gctgaggctg ttcgacttca acaaacaggc tatccagaga 6360 ctgaaggcag aagcccagat gtcaatccag ctgatcaaca aggcagtgaa cgccctgatc 6420 aacgaccagc tgatcatgaa gaaccacctg agagacatta tgggcatccc ctactgtaat 6480 tacagcaagt attggtacct gaaccacact acaaccggga gaacatccct gcccaagtgc 6540 tggctggtca gcaatgggag ttatctgaat gaaacccatt tcagcgacga tatcgaacag 6600 caggctgaca acatgatcac agagatgctg cagaaagagt acatggaaag acagggcaag 6660 acaccactgg gactggtcga tctgttcgtc ttctccacta gcttctatct gatttccatc 6720 ttcctgcacc tggtgaagat ccccactcat aggcacattg tcggcaagag ttgccctaaa 6780 ccccataggc tgaatcacat ggggatttgt agttgcggcc tgtataagca gcctggcgtg 6840 cctgtgaagt ggaagagatg agcgcgcagc gcttagacgt ctcgcgatcg atactagtac 6900 aacctaaatc cattataaaa aacttaggag caaagtgatt gcctcccaag gtccacaatg 6960 acagagacct acgacttcga caagtcggca tgggacatca aagggtcgat cgctccgata 7020 caacccacca cctacagtga tggcaggctg gtgccccagg tcagagtcat agatcctggt 7080 ctaggcgaca ggaaggatga atgctttatg tacatgtttc tgctgggggt tgttgaggac 7140 agcgattccc tagggcctcc aatcgggcga gcatttgggt tcctgccctt aggtgttggc 7200 agatccacag caaagcccga aaaactcctc aaagaggcca ctgagcttga catagttgtt 7260 agacgtacag cagggctcaa tgaaaaactg gtgttctaca acaacacccc actaactctc 7320 ctcacacctt ggagaaaggt cctaacaaca gggagtgtct tcaacgcaaa ccaagtgtgc 7380 aatgcggtta atctgatacc gctcgatacc ccgcagaggt tccgtgttgt ttatatgagc 7440 atcacccgtc tttcggataa cgggtattac accgttccta gaagaatgct ggaattcaga 7500 tcggtcaatg cagtggcctt caacctgctg gtgaccctta ggattgacaa ggcgataggc 7560 cctgggaaga tcatcgacaa tacagagcaa cttcctgagg caacatttat ggtccacatc 7620 gggaacttca ggagaaagaa gagtgaagtc tactctgccg attattgcaa aatgaaaatc 7680 gaaaagatgg gcctggtttt tgcacttggt gggatagggg gcaccagtct tcacattaga 7740 agcacaggca aaatgagcaa gactctccat gcacaactcg ggttcaagaa gaccttatgt 7800 tacccgctga tggatatcaa tgaagacctt aatcgattac tctggaggag cagatgcaag 7860 atagtaagaa tccaggcagt tttgcagcca tcagttcctc aagaattccg catttacgac 7920 gacgtgatca taaatgatga ccaaggacta ttcaaagttc tgtagaccgt agtgcccagc 7980 aatgcccgaa aacgaccccc ctcacaatga cagccagaag gcccggacaa aaaagccccc 8040 tccgaaagac tccacggacc aagcgagagg ccagccagca gccgacggca agcgcgaaca 8100 ccaggcggcc ccagcacaga acagccctga cacaaggcca ccaccagcca ccccaatctg 8160 catcctcctc gtgggacccc cgaggaccaa cccccaaggc tgcccccgat ccaaaccacc 8220 aaccgcatcc ccaccacccc cgggaaagaa acccccagca attggaaggc ccctccccct 8280 cttcctcaac acaagaactc cacaaccgaa ccgcacaagc gaccgaggtg acccaaccgc 8340 aggcatccga ctccctagac agatcctctc tccccggcaa actaaacaaa acttagggcc 8400 aaggaacata cacacccaac agaacccaga ccccggccca cggcgccgcg cccccaaccc 8460 ccgacaacca gagggagccc ccaaccaatc ccgccggctc ccccggtgcc cacaggcagg 8520 gacaccaacc cccgaacaga cccagcaccc aaccatcgac aatccaagac gggggggccc 8580 ccccaaaaaa aggcccccag gggccgacag ccagcaccgc gaggaagccc acccacccca 8640 cacacgacca cggcaaccaa accagaaccc agaccaccct gggccaccag ctcccagact 8700 cggccatcac cccgcagaaa ggaaaggcca caacccgcgc accccagccc cgatccggcg 8760 gggagccacc caacccgaac cagcacccaa gagcgatccc cgaaggaccc ccgaaccgca 8820 aaggacatca gtatcccaca gcctctccaa gtcccccggt ctcctcctct tctcgaaggg 8880 accaaaagat caatccacca cacccgacga cactcaactc cccaccccta aaggagacac 8940 cgggaatccc agaatcaaga ctcatccaat gtccatcatg ggtctcaagg tgaacgtctc 9000 tgccatattc atggcagtac tgttaactct ccaaacaccc accggtcaaa tccattgggg 9060 caatctctct aagatagggg tggtaggaat aggaagtgca agctacaaag ttatgactcg 9120 ttccagccat caatcattag tcataaaatt aatgcccaat ataactctcc tcaataactg 9180 cacgagggta gagattgcag aatacaggag actactgaga acagttttgg aaccaattag 9240 agatgcactt aatgcaatga cccagaatat aagaccggtt cagagtgtag cttcaagtag 9300 gagacacaag agatttgcgg gagtagtcct ggcaggtgcg gccctaggcg ttgccacagc 9360 tgctcagata acagccggca ttgcacttca ccagtccatg ctgaactctc aagccatcga 9420 caatctgaga gcgagcctgg aaactactaa tcaggcaatt gagacaatca gacaagcagg 9480 gcaggagatg atattggctg ttcagggtgt ccaagactac atcaataatg agctgatacc 9540 gtctatgaac caactatctt gtgatttaat cggccagaag ctcgggctca aattgctcag 9600 atactataca gaaatcctgt cattatttgg ccccagttta cgggacccca tatctgcgga 9660 gatatctatc caggctttga gctatgcgct tggaggagac atcaataagg tgttagaaaa 9720 gctcggatac agtggaggtg atttactggg catcttagag agcggaggaa taaaggcccg 9780 gataactcac gtcgacacag agtcctactt cattgtcctc agtatagcct atccgacgct 9840 gtccgagatt aagggggtga ttgtccaccg gctagagggg gtctcgtaca acataggctc 9900 tcaagagtgg tataccactg tgcccaagta tgttgcaacc caagggtacc ttatctcgaa 9960 ttttgatgag tcatcgtgta ctttcatgcc agaggggact gtgtgcagcc aaaatgcctt 10020 gtacccgatg agtcctctgc tccaagaatg cctccggggg tacaccaagt cctgtgctcg 10080 tacactcgta tccgggtctt ttgggaaccg gttcatttta tcacaaggga acctaatagc 10140 caattgtgca tcaatccttt gcaagtgtta cacaacagga acgatcatta atcaagaccc 10200 tgacaagatc ctaacataca ttgctgccga tcactgcccg gtagtcgagg tgaacggcgt 10260 gaccatccaa gtcgggagca ggaggtatcc agacgctgtg tacttgcaca gaattgacct 10320 cggtcctccc atatcattgg agaggttgga cgtagggaca aatctgggga atgcaattgc 10380 taagttggag gatgccaagg aattgttgga gtcatcggac cagatattga ggagtatgaa 10440 aggtttatcg agcactagca tagtctacat cctgattgca gtgtgtcttg gagggttgat 10500 agggatcccc gctttaatat gttgctgcag ggggcgttgt aacaaaaagg gagaacaagt 10560 tggtatgtca agaccaggcc taaagcctga tcttacggga acatcaaaat cctatgtaag 10620 tggtatgtca agaccaggcc taaagcctga tcttacggga acatcaaaat cctatgtaag 10620 gtcgctctga tcctctacaa ctcttgaaac acaaatgtcc cacaagtctc ctcttcgtca 10680 gtcgctctga tcctctacaa ctcttgaaac acaaatgtcc cacaagtctc ctcttcgtca 10680 tcaagcaacc accgcaccca gcatcaagcc cacctgaaat tatctccggc ttccctctgg 10740 tcaagcaacc accgcaccca gcatcaagcc cacctgaaat tatctccggc ttccctctgg 10740 ccgaacaata tcggtagtta atcaaaactt agggtgcaag atcatccaca atgtcaccac 10800 ccgaacaata tcggtagtta atcaaaactt agggtgcaag atcatccaca atgtcaccac 10800 aacgagaccg gataaatgcc ttctacaaag ataaccccca tcccaaggga agtaggatag 10860 aacgagaccg gataaatgcc ttctacaaag ataaccccca tcccaaggga agtaggatag 10860 tcattaacag agaacatctt atgattgata gaccttatgt tttgctggct gttctgtttg 10920 tcattaacag agaacatctt atgattgata gaccttatgt tttgctggct gttctgtttg 10920 tcatgtttct gagcttgatc gggttgctag ccattgcagg cattagactt catcgggcag 10980 tcatgtttct gagcttgatc gggttgctag ccattgcagg cattagactt catcgggcag 10980 ccatctacac cgcagagatc cataaaagcc tcagcaccaa tctagatgta actaactcaa 11040 ccatctacac cgcagagatc cataaaagcc tcagcaccaa tctagatgta actaactcaa 11040 tcgagcatca ggtcaaggac gtgctgacac cactcttcaa aatcatcggt gatgaagtgg 11100 tcgagcatca ggtcaaggac gtgctgacac cactcttcaa aatcatcggt gatgaagtgg 11100 gcctgaggac acctcagaga ttcactgacc tagtgaaatt aatctctgac aagattaaat 11160 gcctgaggac acctcagaga ttcactgacc tagtgaaatt aatctctgac aagattaaat 11160 tccttaatcc ggatagggag tacgacttca gagatctcac ttggtgtatc aacccgccag 11220 tccttaatcc ggatagggag tacgacttca gagatctcac ttggtgtatc aacccgccag 11220 agagaatcaa attggattat gatcaatact gtgcagatgt ggctgctgaa gagctcatga 11280 atgcattggt gaactcaact ctactggaga ccagaacaac caatcagttc ctagctgtct 11340 caaagggaaa ctgctcaggg cccactacaa tcagaggtca attctcaaac atgtcgctgt 11400 ccctgttaga cttgtattta ggtcgaggtt acaatgtgtc atctatagtc actatgacat 11460 cccagggaat gtatggggga acttacctag tggaaaagcc taatctgagc agcaaaaggt 11520 cagagttgtc acaactgagc atgtaccgag tgtttgaagt aggtgttatc agaaatccgg 11580 gtttgggggc tccggtgttc catatgacaa actatcttga gcaaccagtc agtaatgatc 11640 tcagcaactg tatggtggct ttgggggagc tcaaactcgc agccctttgt cacggggaag 11700 attctatcac aattccctat cagggatcag ggaaaggtgt cagcttccag ctcgtcaagc 11760 taggtgtctg gaaatcccca accgacatgc aatcctgggt ccccttatca acggatgatc 11820 cagtgataga caggctttac ctctcatctc acagaggtgt tatcgctgac aatcaagcaa 11880 aatgggctgt cccgacaaca cgaacagatg acaagttgcg aatggagaca tgcttccaac 11940 aggcgtgtaa gggtaaaatc caagcactct gcgagaatcc cgagtgggca ccattgaagg 12000 ataacaggat tccttcatac ggggtcttgt ctgttgatct gagtctgaca gttgagctta 12060 aaatcaaaat tgcttcggga ttcgggccat tgatcacaca cggttcaggg atggacctat 12120 acaaatccaa ccacaacaat gtgtattggc tgactatccc gccaatgaag aacctagcct 12180 taggtgtaat caacacattg gagtggatac cgagattcaa ggttagtccc tacctcttca 12240 ctgtcccaat taaggaagca ggcgaagact gccatgcccc aacataccta cctgcggagg 12300 tggatggtga tgtcaaactc agttccaatc tggtgattct acctggtcaa gatctccaat 12360 atgttttggc aacctacgat acttccaggg ttgaacatgc tgtggtttat tacgtttaca 12420 gcccaagccg ctcattttct tacttttatc cttttaggtt gcctataaag ggggtcccca 12480 tcgaattaca agtggaatgc ttcacatggg accaaaaact ctggtgccgt cacttctgtg 12540 tgcttgcgga ctcagaatct ggtggacata tcactcactc tgggatggtg ggcatgggag 12600 tcagctgcac agtcacccgg gaagatggaa ccaatcgcag atagggctgc tagtgaacca 12660 atcacatgat gtcacccaga catcaggcat acccactagt gtgaaataga catcagaatt 12720 aagaaaaacg tagggtccaa gtggttcccc gttatggact cgctatctgt caaccagatc 12780 ttataccctg aagttcacct agatagcccg atagttacca ataagatagt agccatcctg 12840 gagtatgctc gagtccctca cgcttacagc ctggaggacc ctacactgtg tcagaacatc 12900 aagcaccgcc taaaaaacgg attttccaac caaatgatta taaacaatgt ggaagttggg 12960 aatgtcatca agtccaagct taggagttat ccggcccact ctcatattcc atatccaaat 13020 tgtaatcagg atttatttaa catagaagac aaagagtcaa cgaggaagat ccgtgaactc 13080 ctcaaaaagg ggaattcgct gtactccaaa gtcagtgata aggttttcca atgcttaagg 13140 gacactaact cacggcttgg cctaggctcc gaattgaggg aggacatcaa ggagaaagtt 13200 attaacttgg gagtttacat gcacagctcc cagtggtttg agccctttct gttttggttt 13260 acagtcaaga ctgagatgag gtcagtgatt aaatcacaaa cccatacttg ccataggagg 13320 agacacacac ctgtattctt cactggtagt tcagttgagt tgctaatctc tcgtgacctt 13380 agacacacac ctgtattctt cactggtagt tcagttgagt tgctaatctc tcgtgacctt 13380 gttgctataa tcagtaaaga gtctcaacat gtatattacc tgacatttga actggttttg 13440 gttgctataa tcagtaaaga gtctcaacat gtatattacc tgacatttga actggttttg 13440 atgtattgtg atgtcataga ggggaggtta atgacagaga ccgctatgac tattgatgct 13500 atgtattgtg atgtcataga ggggaggtta atgacagaga ccgctatgac tattgatgct 13500 aggtatacag agcttctagg aagagtcaga tacatgtgga aactgataga tggtttcttc 13560 aggtatacag agcttctagg aagagtcaga tacatgtgga aactgataga tggtttcttc 13560 cctgcactcg ggaatccaac ttatcaaatt gtagccatgc tggagcctct ttcacttgct 13620 cctgcactcg ggaatccaac ttatcaaatt gtagccatgc tggagcctct ttcacttgct 13620 tacctgcagc tgagggatat aacagtagaa ctcagaggtg ctttccttaa ccactgcttt 13680 tacctgcagc tgagggatat aacagtagaa ctcagaggtg ctttccttaa ccactgcttt 13680 actgaaatac atgatgttct tgaccaaaac gggttttctg atgaaggtac ttatcatgag 13740 actgaaatac atgatgttct tgaccaaaac gggttttctg atgaaggtac ttatcatgag 13740 ttaactgaag ctctagatta cattttcata actgatgaca tacatctgac aggggagatt 13800 ttaactgaag ctctagatta cattttcata actgatgaca tacatctgac aggggagatt 13800 ttctcatttt tcagaagttt cggccacccc agacttgaag cagtaacggc tgctgaaaat 13860 ttctcatttt tcagaagttt cggccacccc agacttgaag cagtaacggc tgctgaaaat 13860 gttaggaaat acatgaatca gcctaaagtc attgtgtatg agactctgat gaaaggtcat 13920 gttaggaaat acatgaatca gcctaaagtc attgtgtatg agactctgat gaaaggtcat 13920 gccatatttt gtggaatcat aatcaacggc tatcgtgaca ggcacggagg cagttggcca 13980 gccatatttt gtggaatcat aatcaacggc tatcgtgaca ggcacggagg cagttggcca 13980 ccgctgaccc tccccctgca tgctgcagac acaatccgga atgctcaagc ttcaggtgaa 14040 gggttaacac atgagcagtg cgttgataac tggaaatctt ttgctggagt gaaatttggc 14100 tgctttatgc ctcttagcct ggatagtgat ctgacaatgt acctaaagga caaggcactt 14160 gctgctctcc aaagggaatg ggattcagtt tacccgaaag agttcctgcg ttacgaccct 14220 cccaagggaa ccgggtcacg gaggcttgta gatgttttcc ttaatgattc gagctttgac 14280 ccatatgatg tgataatgta tgttgtaagt ggagcttacc tccatgaccc tgagttcaac 14340 ctgtcttaca gcctgaaaga aaaggagatc aaggaaacag gtagactttt tgctaaaatg 14400 acttacaaaa tgagggcatg ccaagtgatt gctgaaaatc taatctcaaa cgggattggc 14460 aaatatttta aggacaatgg gatggccaag gatgagcacg atttgactaa ggcactccac 14520 actctagctg tctcaggagt ccccaaagat ctcaaagaaa gtcacagggg ggggccagtc 14580 ttaaaaacct actcccgaag cccagtccac acaagtacca ggaacgtgag agcagcaaaa 14640 gggtttatag ggttccctca agtaattcgg caggaccaag acactgatca tccggagaat 14700 atggaagctt acgagacagt cagtgcattt atcacgactg atctcaagaa gtactgcctt 14760 Met Glu Leu Thr Glu Thr Ser Ser Cys Phe Ile Thr Thr Leu Ser Lys Lys Tyr Cys Leu aattggagat atgagaccat cagcttgttt gcacagaggc taaatgagat ttacggattg 14820 Asn Trp Arg Met Glu Thr Ile Ser Leu Phe Cys Gln Arg Ala Asn Glu Ile Tyr Gly Leu ccctcatttt tccagtggct gcataagagg cttgagacct ctgtcctgta tgtaagtgac 14880 Pro Leu Ile Phe Ser Ser Gly Ala His Lys Arg Leu Glu Thr Leu Val Leu Tyr Val Ser Asp cctcattgcc cccccgacct tgacgcccat atcccgttat ataaagtccc caatgatcaa 14940 Pro Ser Ile Ala Pro Pro Asp Leu Asp Ala His Ile Pro Tyr Ile Lys Ser Pro Asn Asp Gln atcttcatta agtaccctat gggaggtata gaagggtatt gtcagaagct gtggaccatc 15000 Ile Phe Ile Lys Tyr Pro Tyr Gly Arg Tyr Glu Gly Ile Val Gln Lys Leu Trp Thr Ile agcaccattc cctatctata cctggctgct tatgagagcg gagtaaggat tgcttcgtta 15060 Ser Thr Ile Pro Pro Tyr Tyr Pro Gly Ala Tyr Glu Ser Glu Tyr Lys Asp Cys Phe Val gtgcaagggg acaatcagac catagccgta acaaaaaggg tacccagcac atggccctac 15120 Val Gln Gly Asp Asn Ser Thr Ile Ala Val Asn Lys Lys Gly Tyr Pro Ala His Trp Pro Tyr aaccttaaga aacgggaagc tgctagagta actagagatt actttgtaat tcttaggcaa 15180 Asn Leu Lys Asn Gly Lys Ala Ala Arg Ser Asn Arg Ile Thr Phe Val Asn Ser Leu Ala aggctacatg atattggcca tcacctcaag gcaaatgaga caattgtttc atcacatttt 15240 Arg Leu Tyr Met Ile Trp Pro Ile Thr Ser Lys Ala Asn Glu Thr Ile Val Phe Ile His Phe tttgtctatt caaaaggaat atattatgat gggctacttg tgtcccaatc actcaagagc 15300 Phe Val Leu Ile Gln Lys Glu Tyr Ile Met Gly Leu Leu Cys Pro Asn Thr Ser Lys Ser atcgcaagat gtgtattctg gtcagagact atagttgatg aaacaagggc agcatgcagt 15360 Ile Ala Arg Met Cys Ile Ser Gly Gln Arg Thr Ser Val Asp Glu Thr Lys Gly Ser Cys Gln aatattgcta caacaatggc taaaagcatc gagagaggtt atgaccgtta ccttgcatat 15420 tccctgaacg tcctaaaagt gatacagcaa attctgatct ctcttggctt cacaatcaat 15480 tcaaccatga cccgggatgt agtcataccc ctcctcacaa acaacgacct cttaataagg 15540 atggcactgt tgcccgctcc tattgggggg atgaattatc tgaatatgag caggctgttt 15600 gtcagaaaca tcggtgatcc agtaacatca tcaattgctg atctcaagag aatgattctc 15660 gcctcactaa tgcctgaaga gaccctccat caagtaatga cacaacaacc gggggactct 15720 tcattcctag actgggctag cgacccttac tcagcaaatc ttgtatgtgt ccagagcatc 15780 actagactcc tcaagaacat aactgcaagg tttgtcctga tccatagtcc aaacccaatg 15840 ttaaaaggat tattccatga tgacagtaaa gaagaggacg agggactggc ggcattcctc 15900 atggacaggc atattatagt acctagggca gctcatgaaa tcctggatca tagtgtcaca 15960 ggggcaagag agtctattgc aggcatgctg gataccacaa aaggcttgat tcgagccagc 16020 atgaggaagg gggggttaac ctctcgagtg ataaccagat tgtccaatta tgactatgaa 16080 caattcagag cagggatggt gctattgaca ggaagaaaga gaaatgtcct cattgacaaa 16140 caattcagag cagggatggt gctattgaca ggaagaaaga gaaatgtcct cattgacaaa 16140 gagtcatgtt cagtgcagct ggcgagagct ctaagaagcc atatgtgggc gaggctagct 16200 gagtcatgtt cagtgcagct ggcgagagct ctaagaagcc atatgtgggc gaggctagct 16200 cgaggacggc ctatttacgg ccttgaggtc cctgatgtac tagaatctat gcgaggccac 16260 cgaggacggc ctatttacgg ccttgaggtc cctgatgtac tagaatctat gcgaggccac 16260 cttattcggc gtcatgagac atgtgtcatc tgcgagtgtg gatcagtcaa ctacggatgg 16320 cttattcggc gtcatgagac atgtgtcatc tgcgagtgtg gatcagtcaa ctacggatgg 16320 ttttttgtcc cctcgggttg ccaactggat gatattgaca aggaaacatc atccttgaga 16380 ttttttgtcc cctcgggttg ccaactggat gatattgaca aggaaacatc atccttgaga 16380 gtcccatata ttggttctac cactgatgag agaacagaca tgaagcttgc cttcgtaaga 16440 gtcccatata ttggttctac cactgatgag agaacagaca tgaagcttgc cttcgtaaga 16440 gccccaagtc gatccttgcg atctgctgtt agaatagcaa cagtgtactc atgggcttac 16500 gccccaagtc gatccttgcg atctgctgtt agaatagcaa cagtgtactc atgggcttac 16500 ggtgatgatg atagctcttg gaacgaagcc tggttgttgg ctaggcaaag ggccaatgtg 16560 ggtgatgatg atagctcttg gaacgaagcc tggttgttgg ctaggcaaag ggccaatgtg 16560 agcctggagg agctaagggt gatcactccc atctcaactt cgactaattt agcgcatagg 16620 agcctggagg agctaagggt gatcactccc atctcaactt cgactaattt agcgcatagg 16620 ttgagggatc gtagcactca agtgaaatac tcaggtacat cccttgtccg agtggcgagg 16680 ttgagggatc gtagcactca agtgaaatac tcaggtacat cccttgtccg agtggcgagg 16680 tataccacaa tctccaacga caatctctca tttgtcatat cagataagaa ggttgatact 16740 tataccacaa tctccaacga caatctctca tttgtcatat cagataagaa ggttgatact 16740 aactttatat accaacaagg aatgcttcta gggttgggtg ttttagaaac attgtttcga 16800 ctcgagaaag ataccggatc atctaacacg gtattacatc ttcacgtcga aacagattgt 16860 tgcgtgatcc cgatgataga tcatcccagg atacccagct cccgcaagct agagctgagg 16920 gcagagctat gtaccaaccc attgatatat gataatgcac ctttaattga cagagatgca 16980 acaaggctat acacccagag ccataggagg caccttgtgg aatttgttac atggtccaca 17040 ccccaactat atcacatttt agctaagtcc acagcactat ctatgattga cctggtaaca 17100 aaatttgaga aggaccatat gaatgaaatt tcagctctca taggggatga cgatatcaat 17160 agtttcataa ctgagtttct gctcatagag ccaagattat tcactatcta cttgggccag 17220 tgtgcggcca tcaattgggc atttgatgta cattatcata gaccatcagg gaaatatcag 17280 atgggtgagc tgttgtcatc gttcctttct agaatgagca aaggagtgtt taaggtgctt 17340 gtcaatgctc taagccaccc aaagatctac aagaaattct ggcattgtgg tattatagag 17400 cctatccatg gtccttcact tgatgctcaa aacttgcaca caactgtgtg caacatggtt 17460 tacacatgct atatgaccta cctcgacctg ttgttgaatg aagagttaga agagttcaca 17520 tttctcttgt gtgaaagcga cgaggatgta gtaccggaca gattcgacaa catccaggca 17580 aaacacttat gtgttctggc agatttgtac tgtcaaccag ggacctgccc accaattcga 17640 ggtctaagac cggtagagaa atgtgcagtt ctaaccgacc atatcaaggc agaggctatg 17700 ttatctccag caggatcttc gtggaacata aatccaatta ttgtagacca ttactcatgc 17760 tctctgactt atctccggcg aggatcgatc aaacagataa gattgagagt tgatccagga 17820 ttcattttcg acgccctcgc tgaggtaaat gtcagtcagc caaagatcgg cagcaacaac 17880 atctcaaata tgagcatcaa ggctttcaga cccccacacg atgatgttgc aaaattgctc 17940 aaagatatca acacaagcaa gcacaatctt cccatttcag ggggcaatct cgccaattat 18000 gaaatccatg ctttccgcag aatcgggttg aactcatctg cttgctacaa agctgttgag 18060 atatcaacat taattaggag atgccttgag ccaggggagg acggcttgtt cttgggtgag 18120 ggatcgggtt ctatgttgat cacttataaa gagatactta aactaaacaa gtgcttctat 18180 aatagtgggg tttccgccaa ttctagatct ggtcaaaggg aattagcacc ctatccctcc 18240 gaagttggcc ttgtcgaaca cagaatggga gtaggtaata ttgtcaaagt gctctttaac 18300 gggaggcccg aagtcacgtg ggtaggcagt gtagattgct tcaatttcat agttagtaat 18360 atccctacct ctagtgtggg gtttatccat tcagatatag agaccttgcc tgacaaagat 18420 actatagaga agctagagga attggcagcc atcttatcga tggctctgct cctgggcaaa 18480 ataggatcaa tactggtgat taagcttatg cctttcagcg gggattttgt tcagggattt 18540 ataagttatg tagggtctca ttatagagaa gtgaaccttg tataccctag atacagcaac 18600 ttcatctcta ctgaatctta tttggttatg acagatctca aggctaaccg gctaatgaat 18660 cctgaaaaga ttaagcagca gataattgaa tcatctgtga ggacttcacc tggacttata 18720 ggtcacatcc tatccattaa gcaactaagc tgcatacaag caattgtggg agacgcagtt 18780 agtagaggtg atatcaatcc tactctgaaa aaacttacac ctatagagca ggtgctgatc 18840 aattgcgggt tggcaattaa cggacctaag ctgtgcaaag aattgatcca ccatgatgtt 18900 gcctcagggc aagatggatt gcttaattct atactcatcc tctacaggga gttggcaaga 18960 ttcaaagaca accaaagaag tcaacaaggg atgttccacg cttaccccgt attggtaagt 19020 agcaggcaac gagaacttat atctaggatc acccgcaaat tctgggggca cattcttctt 19080 tactccggga acaaaaagtt gataaataag tttatccaga atctcaagtc cggctatctg 19140 atactagact tacaccagaa tatcttcgtt aagaatctat ccaagtcaga gaaacagatt 19200 attatgacgg ggggtttgaa acgtgagtgg gtttttaagg taacagtcaa ggagaccaaa 19260 gaatggtata agttagtcgg atacagtgcc ctgattaagg actaattggt tgaactccgg 19320 aaccctaatc ctgccctagg tggttaggca ttatttgcaa tatattaaag aaaactttga 19380 aaatacgaag tttctattcc cagctttgtc tggtggccgg catggtccca gcctcctcgc 19440 tggcgccggc tgggcaacat tccgagggga ccgtcccctc ggtaatggcg aatgggacgc 19500 ggccgatccg gctgctaaca aagcccgaaa ggaagctgag ttggctgctg ccaccgctga 19560 gcaataacta gcataacccc ttggggcctc taaacgggtc ttgaggggtt ttttgctgaa 19620 aggaggaact atatccggat gcggccgcgg gccctatggt acccagcttt tgttcccttt 19680 agtgagggtt aattccgagc ttggcgtaat catggtcata gctgtttcct gtgtgaaatt 19740 gttatccgct cacaattcca cacaacatag gagccggaag cataaagtgt aaagcctggg 19800 gtgcctaatg agtgaggtaa ctcacattaa ttgcgttgcg ctcactgccc gctttccagt 19860 cgggaaacct gtcgtgccag ctgcattaat gaatcggcca acgcgcgggg agaggcggtt 19920 tgcgtattgg gcgctcttcc gcttcctcgc tcactgactc gctgcgctcg gtcgttcggc 19980 tgcggcgagc ggtatcagct cactcaaagg cggtaatacg gttatccaca gaatcagggg 20040 ataacgcagg aaagaacatg tgagcaaaag gccagcaaaa ggccaggaac cgtaaaaagg 20100 ccgcgttgct ggcgtttttc cataggctcg gcccccctga cgagcatcac aaaaatcgac 20160 gctcaagtca gaggtggcga aacccgacag gactataaag ataccaggcg ttcccccctg 20220 gaagctccct cgtgcgctct cctgttccga ccctgccgct taccggatac ctgtccgcct 20280 gaagctccct cgtgcgctct cctgttccga ccctgccgct taccggatac ctgtccgcct 20280 ttctcccttc gggaagcgtg gcgctttctc aatgctcacg ctgtaggtat ctcagttcgg 20340 ttctcccttc gggaagcgtg gcgctttctc aatgctcacg ctgtaggtat ctcagttcgg 20340 tgtaggtcgt tcgctccaag ctgggctgtg tgcacgaacc ccccgttcag cccgaccgct 20400 tgtaggtcgt tcgctccaag ctgggctgtg tgcacgaacc ccccgttcag cccgaccgct 20400 gcgccttatc cggtaactat cgtcttgagt ccaacccggt aagacacgac ttatcgccac 20460 gcgccttatc cggtaactat cgtcttgagt ccaacccggt aagacacgac ttatcgccac 20460 tggcagcagc cactggtaac aggattagca gagcgaggta tgtaggcggt gctacagagt 20520 tggcagcagc cactggtaac aggattagca gagcgaggta tgtaggcggt gctacagagt 20520 tcttgaagtg gtggcctaac tacggctaca ctagaaggac agtatttggt atctgcgctc 20580 tcttgaagtg gtggcctaac tacggctaca ctagaaggac agtatttggt atctgcgctc 20580 tgctgaagcc agttaccttc ggaaaaagag ttggtagctc ttgatccggc aaacaaacca 20640 tgctgaagcc agttaccttc ggaaaaagag ttggtagctc ttgatccggc aaacaaacca 20640 ccgctggtag cggtggtttt tttgtttgca agcagcagat tacgcgcaga aaaaaaggat 20700 ccgctggtag cggtggtttt tttgtttgca agcagcagat tacgcgcaga aaaaaaggat 20700 ctcaagaaga tcctttgatc ttttctacgg ggtctgacgc tcagtggaac gaaaactcac 20760 ctcaagaaga tcctttgatc ttttctacgg ggtctgacgc tcagtggaac gaaaactcac 20760 gttaagggat tttggtcatg agattatcaa aaaggatctt cacctagatc cttttaaatt 20820 gttaagggat tttggtcatg agattatcaa aaaggatctt cacctagatc cttttaaatt 20820 aaaaatgaag ttttaaatca atctaaagta tatatgagta aacttggtct gacagttacc 20880 aaaaatgaag ttttaaatca atctaaagta tatatgagta aacttggtct gacagttacc 20880 aatgcttaat cagtgaggca cctatctcag cgatctgtct atttcgttca tccatagttg 20940 cctgactgcc cgtcgtgtag ataactacga tacgggaggg cttaccatct ggccccagtg 21000 ctgcaatgat accgcgagac ccacgctcac cggctccaga tttatcagca ataaaccagc 21060 cagccggaag ggccgagcgc agaagtggtc ctgcaacttt atccgcctcc atccagtcta 21120 ttaattgttg ccgggaagct agagtaagta gttcgccagt taatagtttg cgcaacgttg 21180 ttgccattgc tacaggcatc gtggtgtcac gctcgtcgtt tggtatggct tcattcagct 21240 ccggttccca acgatcaagg cgagttacat gatcccccat gttgtgaaaa aaagcggtta 21300 gctccttcgg tcctccgatc gttgtcagaa gtaagttggc cgcagtgtta tcactcatgc 21360 ttatggcagc actgcataat tctcttactg tcatgccatc cgtaagatgc ttttctgtga 21420 ctggtgagta ctcaaccaag tcattctgag aatagtgtat gcggcgaccg agttgctctt 21480 gcccggcgtc aatacgggat aataccgcgc cacatagcag aactttaaaa gtgctcatca 21540 ttggaaaacg ttcttcgggg cgaaaactct caaggatctt accgctgttg agatccagtt 21600 cgatgtaacc cactcgtgca cccaactgat cttcagcatc ttttactttc accagcgttt 21660 cgatgtaacc cactcgtgca cccaactgat cttcagcatc ttttactttc accagcgttt 21660 ctgggtgagc aaaaacagga aggcaaaatg ccgcaaaaaa gggaataagg gcgacacgga 21720 ctgggtgagc aaaaacagga aggcaaaatg ccgcaaaaaa gggaataagg gcgacacgga 21720 aatgttgaat actcatactc ttcctttttc aatattattg aagcatttat cagggttatt 21780 aatgttgaat actcatactc ttcctttttc aatattattg aagcatttat cagggttatt 21780 gtctcatgag cggatacata tttgaatgta tttagaaaaa taaacaaata ggggttccgc 21840 gtctcatgag cggatacata tttgaatgta tttagaaaaa taaacaaata ggggttccgc 21840 gcacatttcc ccgaaaagtg ccacctgaaa ttgtaaacgt taatattttg ttaaaattcg 21900 gcacatttcc ccgaaaagtg ccacctgaaa ttgtaaacgt taatattttg ttaaaattcg 21900 cgttaaattt ttgttaaatc agctcatttt ttaaccaata ggccgaaatc ggcaaaatcc 21960 cgttaaattt ttgttaaatc agctcatttt ttaaccaata ggccgaaatc ggcaaaatcc 21960 cttataaatc aaaagaatag accgagatag ggttgagtgt tgttccagtt tggaacaaga 22020 cttataaatc aaaagaatag accgagatag ggttgagtgt tgttccagtt tggaacaaga 22020 gtccactatt aaagaacgtg gactccaacg tcaaagggcg aaaaaccgtc tatcagggcg 22080 gtccactatt aaagaacgtg gactccaacg tcaaagggcg aaaaaccgtc tatcagggcg 22080 atggcccact acgtgaacca tcaccctaat caagtttttt ggggtcgagg tgccgtaaag 22140 atggcccact acgtgaacca tcaccctaat caagtttttt ggggtcgagg tgccgtaaag 22140 cactaaatcg gaaccctaaa gggagccccc gatttagagc ttgacgggga aagccggcga 22200 cactaaatcg gaaccctaaa gggagccccc gatttagagc ttgacgggga aagccggcga 22200 acgtggcgag aaaggaaggg aagaaagcga aaggagcggg cgctagggcg ctggcaagtg 22260 acgtggcgag aaaggaaggg aagaaagcga aaggagcggg cgctagggcg ctggcaagtg 22260 tagcggtcac gctgcgcgta accaccacac ccgccgcgct taatgcgccg ctacagggcg 22320 cgtcccattc gccattcagg ctgcgcaact gttgggaagg gcgatcggtg cgggcctctt 22380 cgctattacg ccagccaccg cggtg 22405 <210> 12 <211> 21007 <212> DNA <213> Artificial Sequence <220> <223> Plasmid MeV-Z-GPC <400> 12 gcggccgcta atacgactca ctatagggcc aactttgttt ggtctgatga gtccgtgagg 60 acgaaacccg gagtcccggg tcaccaaaca aagttgggta aggatagttc aatcaatgat 120 catcttctag tgcacttagg attcaagatc ctattatcag ggacaagagc aggattaggg 180 atatccgaga cgcgtacgat gggcaataag caggcaaagg cacccgaaag caaggattca 240 cctagagcat cactgattcc cgacgcaact catctggggc cacagttctg caaatcctgt 300 tggttcgaga acaaaggcct ggtggagtgc aataaccact acctgtgcct gaactgtctg 360 acactgctgc tgagtgtgag caacagatgc ccaatctgca agatgcctct gccaacaaag 420 ctgaggcctt ctgctgcacc caccgcacca ccaactggag ccgcagacag cattagaccc 480 cccccatact caccataagc gcgcagcgct tagacgtctc gcgatcgatt agtgcgagag 540 gccgagggcc agaacaacat ccgcctacca tccatcattg ttataaaaaa cttaggattc 600 aagatcctat tatcagggac aagagcagga ttagggatat ccgagatggc cacactttta 660 aggagcttag cattgttcaa aagaaacaag gacaaaccac ccattacatc aggatccggt 720 ggagccatca gaggaatcaa acacattatt atagtaccaa tccctggaga ttcctcaatt 780 accactcgat ccagacttct ggaccggttg gtgaggttaa ttggaaaccc ggatgtgagc 840 gggcccaaac taacaggggc actaataggt atattatcct tatttgtgga gtctccaggt 900 caattgattc agaggatcac cgatgaccct gacgttagca taaggctgtt agaggttgtc 960 cagagtgacc agtcacaatc tggccttacc ttcgcatcaa gaggtaccaa catggaggat 1020 gaggcggacc aatacttttc acatgatgat ccaattagta gtgatcaatc caggttcgga 1080 tggttcggga acaaggaaat ctcagatatt gaagtgcaag accctgaggg attcaacatg 1140 attctgggta ccatcctagc ccaaatttgg gtcttgctcg caaaggcggt tacggcccca 1200 gacacggcag ctgattcgga gctaagaagg tggataaagt acacccaaca aagaagggta 1260 gttggtgaat ttagattgga gagaaaatgg ttggatgtgg tgaggaacag gattgccgag 1320 gacctctcct tacgccgatt catggtcgct ctaatcctgg atatcaagag aacacccgga 1380 aacaaaccca ggattgctga aatgatatgt gacattgata catatatcgt agaggcagga 1440 ttagccagtt ttatcctgac tattaagttt gggatagaaa ctatgtatcc tgctcttgga 1500 ctgcatgaat ttgctggtga gttatccaca cttgagtcct tgatgaacct ttaccagcaa 1560 atgggggaaa ctgcacccta catggtaatc ctggagaact caattcagaa caagttcagt 1620 gcaggatcat accctctgct ctggagctat gccatgggag taggagtgga acttgaaaac 1680 tccatgggag gtttgaactt tggccgatct tactttgatc cagcatattt tagattaggg 1740 caagagatgg taaggaggtc agctggaaag gtcagttcca cattggcatc tgaactcggt 1800 atcactgccg aggatgcaag gcttgtttca gagattgcaa tgcatactac tgaggacaag 1860 atcagtagag cggttggacc cagacaagcc caagtatcat ttctacacgg tgatcaaagt 1920 gagaatgagc taccgagatt ggggggcaag gaagatagga gggtcaaaca gagtcgagga 1980 gaagccaggg agagctacag agaaaccggg cccagcagag caagtgatgc gagagctgcc 2040 catcttccaa ccggcacacc cctagacatt gacactgcaa cggagtccag ccaagatccg 2100 caggacagtc gaaggtcagc tgacgccctg cttaggctgc aagccatggc aggaatctcg 2160 gaagaacaag gctcagacac ggacacccct atagtgtaca atgacagaaa tcttctagac 2220 taggtgcgag aggccgaggg ccagaacaac atccgcctac catccatcat tgttataaaa 2280 aacttaggaa ccaggtccac acagccgcca gcccatcaac catccactcc cacgattgga 2340 gccaatggca gaagagcagg cacgccatgt caaaaacgga ctggaatgca tccgggctct 2400 caaggccgag cccatcggct cactggccat cgaggaagct atggcagcat ggtcagaaat 2460 atcagacaac ccaggacagg agcgagccac ctgcagggaa gagaaggcag gcagttcggg 2520 tctcagcaaa ccatgcctct cagcaattgg atcaactgaa ggcggtgcac ctcgcatccg 2580 cggtcaggga cctggagaga gcgatgacga cgctgaaact ttgggaatcc ccccaagaaa 2640 tctccaggca tcaagcactg ggttacagtg ttattacgtt tatgatcaca gcggtgaagc 2700 ggttaaggga atccaagatg ctgactctat catggttcaa tcaggccttg atggtgatag 2760 caccctctca ggaggagaca atgaatctga aaacagcgat gtggatattg gcgaacctga 2820 taccgaggga tatgctatca ctgaccgggg atctgctccc atctctatgg ggttcagggc 2880 ttctgatgtt gaaactgcag aaggagggga gatccacgag ctcctgagac tccaatccag 2940 aggcaacaac tttccgaagc ttgggaaaac tctcaatgtt cctccgcccc cggaccccgg 3000 tagggccagc acttccggga cacccattaa aaagggcaca gacgcgagat tagcctcatt 3060 tggaacggag atcgcgtctt tattgacagg tggtgcaacc caatgtgctc gaaagtcacc 3120 ctcggaacca tcagggccag gtgcacctgc ggggaatgtc cccgagtgtg tgagcaatgc 3180 cgcactgata caggagtgga cacccgaatc tggtaccaca atctccccga gatcccagaa 3240 taatgaagaa gggggagact attatgatga tgagctgttc tctgatgtcc aagatattaa 3300 aacagccttg gccaaaatac acgaggataa tcagaagata atctccaagc tagaatcact 3360 gctgttattg aagggagaag ttgagtcaat taagaagcag atcaacaggc aaaatatcag 3420 catatccacc ctggaaggac acctctcaag catcatgatc gccattcctg gacttgggaa 3480 ggatcccaac gaccccactg cagatgtcga aatcaatccc gacttgaaac ccatcatagg 3540 cagagattca ggccgagcac tggccgaagt tctcaagaaa cccgttgcca gccgacaact 3600 ccaaggaatg acaaatggac ggaccagttc cagaggacag ctgctgaagg aatttcagct 3660 aaagccgatc gggaaaaaga tgagctcagc cgtcgggttt gttcctgaca ccggccctgc 3720 atcacgcagt gtaatccgct ccattataaa atccagccgg ctagaggagg atcggaagcg 3780 ttacctgatg actctccttg atgatatcaa aggagccaat gatcttgcca agttccacca 3840 gatgctgatg aagataataa tgaagtagct acagctcaac ttacctgcca accccatgcc 3900 agtcgaccca actagcctac cctccatcat tgttataaaa aacttaggaa ccaggtccac 3960 acagccgcca gcccatcaac gcgtacgatg ggccagattg tcacattctt tcaggaagtg 4020 ccacacgtca ttgaggaggt catgaacatc gtgctgattg ctctgtcagt gctggcagtg 4080 ctgaaaggac tgtacaactt cgctacctgt ggactggtgg gactggtcac attcctgctg 4140 ctgtgcggca gaagttgcac tacctcactg tacaaaggag tgtacgagct gcagactctg 4200 gaactgaaca tggagacact gaatatgaca atgcctctga gctgcaccaa gaataatagc 4260 caccactata tcatggtcgg gaacgaaacc ggcctggaac tgaccctgac aaacaccagc 4320 atcattaacc acaagttctg caatctgagc gacgctcaca agaagaacct gtatgaccac 4380 gctctgatgt ccatcatcag tacctttcac ctgtccatcc ccaatttcaa ccagtacgag 4440 gcaatgtcat gcgacttcaa cgggggcaag atcagtgtcc agtacaacct gagccactcc 4500 tacgccggcg acgcagccaa ccactgcgga actgtcgcca atggcgtgct gcagacattc 4560 atgaggatgg catggggggg atcttacatc gcactggata gcggcagggg caattgggat 4620 tgcatcatga cttcctatca gtatctgatt atccagaata ctacatggga ggatcattgc 4680 cagttcagtc ggcccagccc tattggatat ctggggctgc tgtcacagag aacacgggat 4740 atctatattt caagacgcct gctgggcaca ttcacttgga cactgtcaga cagtgagggc 4800 aaggatactc cagggggcta ctgcctgaca cgatggatgc tgatcgaagc agagctgaaa 4860 tgcttcggca ataccgcagt ggccaagtgc aacgagaaac acgacgagga gttctgcgac 4920 atgctgaggc tgttcgactt caacaaacag gctatccaga gactgaaggc agaagcccag 4980 atgtcaatcc agctgatcaa caaggcagtg aacgccctga tcaacgacca gctgatcatg 5040 aagaaccacc tgagagacat tatgggcatc ccctactgta attacagcaa gtattggtac 5100 ctgaaccaca ctacaaccgg gagaacatcc ctgcccaagt gctggctggt cagcaatggg 5160 agttatctga atgaaaccca tttcagcgac gatatcgaac agcaggctga caacatgatc 5220 acagagatgc tgcagaaaga gtacatggaa agacagggca agacaccact gggactggtc 5280 gatctgttcg tcttctccac tagcttctat ctgatttcca tcttcctgca cctggtgaag 5340 atccccactc ataggcacat tgtcggcaag agttgcccta aaccccatag gctgaatcac 5400 atggggattt gtagttgcgg cctgtataag cagcctggcg tgcctgtgaa gtggaagaga 5460 tgagcgcgca gcgcttagac gtctcgcgat cgatactagt acaacctaaa tccattataa 5520 aaaacttagg agcaaagtga ttgcctccca aggtccacaa tgacagagac ctacgacttc 5580 gacaagtcgg catgggacat caaagggtcg atcgctccga tacaacccac cacctacagt 5640 gatggcaggc tggtgcccca ggtcagagtc atagatcctg gtctaggcga caggaaggat 5700 gaatgcttta tgtacatgtt tctgctgggg gttgttgagg acagcgattc cctagggcct 5760 ccaatcgggc gagcatttgg gttcctgccc ttaggtgttg gcagatccac agcaaagccc 5820 gaaaaactcc tcaaagaggc cactgagctt gacatagttg ttagacgtac agcagggctc 5880 aatgaaaaac tggtgttcta caacaacacc ccactaactc tcctcacacc ttggagaaag 5940 gtcctaacaa cagggagtgt cttcaacgca aaccaagtgt gcaatgcggt taatctgata 6000 ccgctcgata ccccgcagag gttccgtgtt gtttatatga gcatcacccg tctttcggat 6060 aacgggtatt acaccgttcc tagaagaatg ctggaattca gatcggtcaa tgcagtggcc 6120 ttcaacctgc tggtgaccct taggattgac aaggcgatag gccctgggaa gatcatcgac 6180 aatacagagc aacttcctga ggcaacattt atggtccaca tcgggaactt caggagaaag 6240 aagagtgaag tctactctgc cgattattgc aaaatgaaaa tcgaaaagat gggcctggtt 6300 tttgcacttg gtgggatagg gggcaccagt cttcacatta gaagcacagg caaaatgagc 6360 aagactctcc atgcacaact cgggttcaag aagaccttat gttacccgct gatggatatc 6420 aatgaagacc ttaatcgatt actctggagg agcagatgca agatagtaag aatccaggca 6480 gttttgcagc catcagttcc tcaagaattc cgcatttacg acgacgtgat cataaatgat 6540 gaccaaggac tattcaaagt tctgtagacc gtagtgccca gcaatgcccg aaaacgaccc 6600 ccctcacaat gacagccaga aggcccggac aaaaaagccc cctccgaaag actccacgga 6660 ccaagcgaga ggccagccag cagccgacgg caagcgcgaa caccaggcgg ccccagcaca 6720 gaacagccct gacacaaggc caccaccagc caccccaatc tgcatcctcc tcgtgggacc 6780 cccgaggacc aacccccaag gctgcccccg atccaaacca ccaaccgcat ccccaccacc 6840 cccgggaaag aaacccccag caattggaag gcccctcccc ctcttcctca acacaagaac 6900 tccacaaccg aaccgcacaa gcgaccgagg tgacccaacc gcaggcatcc gactccctag 6960 acagatcctc tctccccggc aaactaaaca aaacttaggg ccaaggaaca tacacaccca 7020 acagaaccca gaccccggcc cacggcgccg cgcccccaac ccccgacaac cagagggagc 7080 ccccaaccaa tcccgccggc tcccccggtg cccacaggca gggacaccaa cccccgaaca 7140 gacccagcac ccaaccatcg acaatccaag acgggggggc ccccccaaaa aaaggccccc 7200 aggggccgac agccagcacc gcgaggaagc ccacccaccc cacacacgac cacggcaacc 7260 aaaccagaac ccagaccacc ctgggccacc agctcccaga ctcggccatc accccgcaga 7320 aaggaaaggc cacaacccgc gcaccccagc cccgatccgg cggggagcca cccaacccga 7380 accagcaccc aagagcgatc cccgaaggac ccccgaaccg caaaggacat cagtatccca 7440 cagcctctcc aagtcccccg gtctcctcct cttctcgaag ggaccaaaag atcaatccac 7500 cacacccgac gacactcaac tccccacccc taaaggagac accgggaatc ccagaatcaa 7560 gactcatcca atgtccatca tgggtctcaa ggtgaacgtc tctgccatat tcatggcagt 7620 actgttaact ctccaaacac ccaccggtca aatccattgg ggcaatctct ctaagatagg 7680 ggtggtagga ataggaagtg caagctacaa agttatgact cgttccagcc atcaatcatt 7740 agtcataaaa ttaatgccca atataactct cctcaataac tgcacgaggg tagagattgc 7800 agaatacagg agactactga gaacagtttt ggaaccaatt agagatgcac ttaatgcaat 7860 gacccagaat ataagaccgg ttcagagtgt agcttcaagt aggagacaca agagatttgc 7920 gggagtagtc ctggcaggtg cggccctagg cgttgccaca gctgctcaga taacagccgg 7980 cattgcactt caccagtcca tgctgaactc tcaagccatc gacaatctga gagcgagcct 8040 ggaaactact aatcaggcaa ttgagacaat cagacaagca gggcaggaga tgatattggc 8100 tgttcagggt gtccaagact acatcaataa tgagctgata ccgtctatga accaactatc 8160 ttgtgattta atcggccaga agctcgggct caaattgctc agatactata cagaaatcct 8220 gtcattattt ggccccagtt tacgggaccc catatctgcg gagatatcta tccaggcttt 8280 gagctatgcg cttggaggag acatcaataa ggtgttagaa aagctcggat acagtggagg 8340 tgatttactg ggcatcttag agagcggagg aataaaggcc cggataactc acgtcgacac 8400 agagtcctac ttcattgtcc tcagtatagc ctatccgacg ctgtccgaga ttaagggggt 8460 gattgtccac cggctagagg gggtctcgta caacataggc tctcaagagt ggtataccac 8520 tgtgcccaag tatgttgcaa cccaagggta ccttatctcg aattttgatg agtcatcgtg 8580 tactttcatg ccagagggga ctgtgtgcag ccaaaatgcc ttgtacccga tgagtcctct 8640 gctccaagaa tgcctccggg ggtacaccaa gtcctgtgct cgtacactcg tatccgggtc 8700 ttttgggaac cggttcattt tatcacaagg gaacctaata gccaattgtg catcaatcct 8760 ttgcaagtgt tacacaacag gaacgatcat taatcaagac cctgacaaga tcctaacata 8820 cattgctgcc gatcactgcc cggtagtcga ggtgaacggc gtgaccatcc aagtcgggag 8880 caggaggtat ccagacgctg tgtacttgca cagaattgac ctcggtcctc ccatatcatt 8940 ggagaggttg gacgtaggga caaatctggg gaatgcaatt gctaagttgg aggatgccaa 9000 ggaattgttg gagtcatcgg accagatatt gaggagtatg aaaggtttat cgagcactag 9060 catagtctac atcctgattg cagtgtgtct tggagggttg atagggatcc ccgctttaat 9120 atgttgctgc agggggcgtt gtaacaaaaa gggagaacaa gttggtatgt caagaccagg 9180 cctaaagcct gatcttacgg gaacatcaaa atcctatgta aggtcgctct gatcctctac 9240 aactcttgaa acacaaatgt cccacaagtc tcctcttcgt catcaagcaa ccaccgcacc 9300 cagcatcaag cccacctgaa attatctccg gcttccctct ggccgaacaa tatcggtagt 9360 taatcaaaac ttagggtgca agatcatcca caatgtcacc acaacgagac cggataaatg 9420 ccttctacaa agataacccc catcccaagg gaagtaggat agtcattaac agagaacatc 9480 ttatgattga tagaccttat gttttgctgg ctgttctgtt tgtcatgttt ctgagcttga 9540 tcgggttgct agccattgca ggcattagac ttcatcgggc agccatctac accgcagaga 9600 tccataaaag cctcagcacc aatctagatg taactaactc aatcgagcat caggtcaagg 9660 acgtgctgac accactcttc aaaatcatcg gtgatgaagt gggcctgagg acacctcaga 9720 gattcactga cctagtgaaa ttaatctctg acaagattaa attccttaat ccggataggg 9780 agtacgactt cagagatctc acttggtgta tcaacccgcc agagagaatc aaattggatt 9840 atgatcaata ctgtgcagat gtggctgctg aagagctcat gaatgcattg gtgaactcaa 9900 ctctactgga gaccagaaca accaatcagt tcctagctgt ctcaaaggga aactgctcag 9960 ggcccactac aatcagaggt caattctcaa acatgtcgct gtccctgtta gacttgtatt 10020 taggtcgagg ttacaatgtg tcatctatag tcactatgac atcccaggga atgtatgggg 10080 gaacttacct agtggaaaag cctaatctga gcagcaaaag gtcagagttg tcacaactga 10140 gcatgtaccg agtgtttgaa gtaggtgtta tcagaaatcc gggtttgggg gctccggtgt 10200 tccatatgac aaactatctt gagcaaccag tcagtaatga tctcagcaac tgtatggtgg 10260 ctttggggga gctcaaactc gcagcccttt gtcacgggga agattctatc acaattccct 10320 atcagggatc agggaaaggt gtcagcttcc agctcgtcaa gctaggtgtc tggaaatccc 10380 caaccgacat gcaatcctgg gtccccttat caacggatga tccagtgata gacaggcttt 10440 acctctcatc tcacagaggt gttatcgctg acaatcaagc aaaatgggct gtcccgacaa 10500 cacgaacaga tgacaagttg cgaatggaga catgcttcca acaggcgtgt aagggtaaaa 10560 cacgaacaga tgacaagttg cgaatggaga catgcttcca acaggcgtgt aagggtaaaa 10560 tccaagcact ctgcgagaat cccgagtggg caccattgaa ggataacagg attccttcat 10620 tccaagcact ctgcgagaat cccgagtggg caccattgaa ggataacagg attccttcat 10620 acggggtctt gtctgttgat ctgagtctga cagttgagct taaaatcaaa attgcttcgg 10680 acggggtctt gtctgttgat ctgagtctga cagttgagct taaaatcaaa attgcttcgg 10680 gattcgggcc attgatcaca cacggttcag ggatggacct atacaaatcc aaccacaaca 10740 gattcgggcc attgatcaca cacggttcag ggatggacct atacaaatcc aaccacaaca 10740 atgtgtattg gctgactatc ccgccaatga agaacctagc cttaggtgta atcaacacat 10800 atgtgtattg gctgactatc ccgccaatga agaacctagc cttaggtgta atcaacacat 10800 tggagtggat accgagattc aaggttagtc cctacctctt cactgtccca attaaggaag 10860 tggagtggat accgagattc aaggttagtc cctacctctt cactgtccca attaaggaag 10860 caggcgaaga ctgccatgcc ccaacatacc tacctgcgga ggtggatggt gatgtcaaac 10920 caggcgaaga ctgccatgcc ccaacatacc tacctgcgga ggtggatggt gatgtcaaac 10920 tcagttccaa tctggtgatt ctacctggtc aagatctcca atatgttttg gcaacctacg 10980 tcagttccaa tctggtgatt ctacctggtc aagatctcca atatgttttg gcaacctacg 10980 atacttccag ggttgaacat gctgtggttt attacgttta cagcccaagc cgctcatttt 11040 atacttccag ggttgaacat gctgtggttt attacgttta cagcccaagc cgctcatttt 11040 cttactttta tccttttagg ttgcctataa agggggtccc catcgaatta caagtggaat 11100 cttactttta tccttttagg ttgcctataa agggggtccc catcgaatta caagtggaat 11100 gcttcacatg ggaccaaaaa ctctggtgcc gtcacttctg tgtgcttgcg gactcagaat 11160 gcttcacatg ggaccaaaaa ctctggtgcc gtcacttctg tgtgcttgcg gactcagaat 11160 ctggtggaca tatcactcac tctgggatgg tgggcatggg agtcagctgc acagtcaccc 11220 gggaagatgg aaccaatcgc agatagggct gctagtgaac caatcacatg atgtcaccca 11280 gacatcaggc atacccacta gtgtgaaata gacatcagaa ttaagaaaaa cgtagggtcc 11340 aagtggttcc ccgttatgga ctcgctatct gtcaaccaga tcttataccc tgaagttcac 11400 ctagatagcc cgatagttac caataagata gtagccatcc tggagtatgc tcgagtccct 11460 cacgcttaca gcctggagga ccctacactg tgtcagaaca tcaagcaccg cctaaaaaac 11520 ggattttcca accaaatgat tataaacaat gtggaagttg ggaatgtcat caagtccaag 11580 cttaggagtt atccggccca ctctcatatt ccatatccaa attgtaatca ggatttattt 11640 aacatagaag acaaagagtc aacgaggaag atccgtgaac tcctcaaaaa ggggaattcg 11700 ctgtactcca aagtcagtga taaggttttc caatgcttaa gggacactaa ctcacggctt 11760 ggcctaggct ccgaattgag ggaggacatc aaggagaaag ttattaactt gggagtttac 11820 atgcacagct cccagtggtt tgagcccttt ctgttttggt ttacagtcaa gactgagatg 11880 aggtcagtga ttaaatcaca aacccatact tgccatagga ggagacacac acctgtattc 11940 aggtcagtga ttaaatcaca aacccatact tgccatagga ggagacacac acctgtattc 11940 ttcactggta gttcagttga gttgctaatc tctcgtgacc ttgttgctat aatcagtaaa 12000 ttcactggta gttcagttga gttgctaatc tctcgtgacc ttgttgctat aatcagtaaa 12000 gagtctcaac atgtatatta cctgacattt gaactggttt tgatgtattg tgatgtcata 12060 gagtctcaac atgtatatta cctgacattt gaactggttt tgatgtattg tgatgtcata 12060 gaggggaggt taatgacaga gaccgctatg actattgatg ctaggtatac agagcttcta 12120 gaggggaggt taatgacaga gaccgctatg actattgatg ctaggtatac agagcttcta 12120 ggaagagtca gatacatgtg gaaactgata gatggtttct tccctgcact cgggaatcca 12180 ggaagagtca gatacatgtg gaaactgata gatggtttct tccctgcact cgggaatcca 12180 acttatcaaa ttgtagccat gctggagcct ctttcacttg cttacctgca gctgagggat 12240 acttatcaaa ttgtagccat gctggagcct ctttcacttg cttacctgca gctgagggat 12240 ataacagtag aactcagagg tgctttcctt aaccactgct ttactgaaat acatgatgtt 12300 ataacagtag aactcagagg tgctttcctt aaccactgct ttactgaaat acatgatgtt 12300 cttgaccaaa acgggttttc tgatgaaggt acttatcatg agttaactga agctctagat 12360 cttgaccaaa acgggttttc tgatgaaggt acttatcatg agttaactga agctctagat 12360 tacattttca taactgatga catacatctg acaggggaga ttttctcatt tttcagaagt 12420 tacattttca taactgatga catacatctg acaggggaga ttttctcatt tttcagaagt 12420 ttcggccacc ccagacttga agcagtaacg gctgctgaaa atgttaggaa atacatgaat 12480 ttcggccacc ccagacttga agcagtaacg gctgctgaaa atgttaggaa atacatgaat 12480 cagcctaaag tcattgtgta tgagactctg atgaaaggtc atgccatatt ttgtggaatc 12540 cagcctaaag tcattgtgta tgagactctg atgaaaggtc atgccatatt ttgtggaatc 12540 ataatcaacg gctatcgtga caggcacgga ggcagttggc caccgctgac cctccccctg 12600 catgctgcag acacaatccg gaatgctcaa gcttcaggtg aagggttaac acatgagcag 12660 tgcgttgata actggaaatc ttttgctgga gtgaaatttg gctgctttat gcctcttagc 12720 ctggatagtg atctgacaat gtacctaaag gacaaggcac ttgctgctct ccaaagggaa 12780 tgggattcag tttacccgaa agagttcctg cgttacgacc ctcccaaggg aaccgggtca 12840 cggaggcttg tagatgtttt ccttaatgat tcgagctttg acccatatga tgtgataatg 12900 tatgttgtaa gtggagctta cctccatgac cctgagttca acctgtctta cagcctgaaa 12960 gaaaaggaga tcaaggaaac aggtagactt tttgctaaaa tgacttacaa aatgagggca 13020 tgccaagtga ttgctgaaaa tctaatctca aacgggattg gcaaatattt taaggacaat 13080 gggatggcca aggatgagca cgatttgact aaggcactcc acactctagc tgtctcagga 13140 gtccccaaag atctcaaaga aagtcacagg ggggggccag tcttaaaaac ctactcccga 13200 agcccagtcc acacaagtac caggaacgtg agagcagcaa aagggtttat agggttccct 13260 caagtaattc ggcaggacca agacactgat catccggaga atatggaagc ttacgagaca 13320 caagtaattc ggcaggacca agacactgat catccggaga atatggaagc ttacgagaca 13320 gtcagtgcat ttatcacgac tgatctcaag aagtactgcc ttaattggag atatgagacc 13380 gtcagtgcat ttatcacgac tgatctcaag aagtactgcc ttaattggag atatgagacc 13380 atcagcttgt ttgcacagag gctaaatgag atttacggat tgccctcatt tttccagtgg 13440 atcagcttgt ttgcacagag gctaaatgag atttacggat tgccctcatt tttccagtgg 13440 ctgcataaga ggcttgagac ctctgtcctg tatgtaagtg accctcattg cccccccgac 13500 ctgcataaga ggcttgagac ctctgtcctg tatgtaagtg accctcattg cccccccgac 13500 cttgacgccc atatcccgtt atataaagtc cccaatgatc aaatcttcat taagtaccct 13560 cttgacgccc atatcccgtt atataaagtc cccaatgatc aaatcttcat taagtaccct 13560 atgggaggta tagaagggta ttgtcagaag ctgtggacca tcagcaccat tccctatcta 13620 atgggaggta tagaagggta ttgtcagaag ctgtggacca tcagcaccat tccctatcta 13620 tacctggctg cttatgagag cggagtaagg attgcttcgt tagtgcaagg ggacaatcag 13680 tacctggctg cttatgagag cggagtaagg attgcttcgt tagtgcaagg ggacaatcag 13680 accatagccg taacaaaaag ggtacccagc acatggccct acaaccttaa gaaacgggaa 13740 accatagccg taacaaaaag ggtacccagc acatggccct acaaccttaa gaaacgggaa 13740 gctgctagag taactagaga ttactttgta attcttaggc aaaggctaca tgatattggc 13800 gctgctagag taactagaga ttactttgta attcttaggc aaaggctaca tgatattggc 13800 catcacctca aggcaaatga gacaattgtt tcatcacatt tttttgtcta ttcaaaagga 13860 catcacctca aggcaaatga gacaattgtt tcatcacatt tttttgtcta ttcaaaagga 13860 atatattatg atgggctact tgtgtcccaa tcactcaaga gcatcgcaag atgtgtattc 13920 atatattatg atgggctact tgtgtcccaa tcactcaaga gcatcgcaag atgtgtattc 13920 tggtcagaga ctatagttga tgaaacaagg gcagcatgca gtaatattgc tacaacaatg 13980 tggtcagaga ctatagttga tgaaacaagg gcagcatgca gtaatattgc tacaacaatg 13980 gctaaaagca tcgagagagg ttatgaccgt taccttgcat attccctgaa cgtcctaaaa 14040 gctaaaagca tcgagagagg ttatgaccgt taccttgcat attccctgaa cgtcctaaaa 14040 gtgatacagc aaattctgat ctctcttggc ttcacaatca attcaaccat gacccgggat 14100 gtgatacagc aaattctgat ctctcttggc ttcacaatca attcaaccat gacccgggat 14100 gtagtcatac ccctcctcac aaacaacgac ctcttaataa ggatggcact gttgcccgct 14160 gtagtcatac ccctcctcac aaacaacgac ctcttaataa ggatggcact gttgcccgct 14160 cctattgggg ggatgaatta tctgaatatg agcaggctgt ttgtcagaaa catcggtgat 14220 cctattgggg ggatgaatta tctgaatatg agcaggctgt ttgtcagaaa catcggtgat 14220 ccagtaacat catcaattgc tgatctcaag agaatgattc tcgcctcact aatgcctgaa 14280 ccagtaacat catcaattgc tgatctcaag agaatgattc tcgcctcact aatgcctgaa 14280 gagaccctcc atcaagtaat gacacaacaa ccgggggact cttcattcct agactgggct 14340 gagaccctcc atcaagtaat gacacaacaa ccgggggact cttcattcct agactgggct 14340 agcgaccctt actcagcaaa tcttgtatgt gtccagagca tcactagact cctcaagaac 14400 agcgaccctt actcagcaaa tcttgtatgt gtccagagca tcactagact cctcaagaac 14400 ataactgcaa ggtttgtcct gatccatagt ccaaacccaa tgttaaaagg attattccat 14460 ataactgcaa ggtttgtcct gatccatagt ccaaacccaa tgttaaaagg attattccat 14460 gatgacagta aagaagagga cgagggactg gcggcattcc tcatggacag gcatattata 14520 gatgacagta aagaagagga cgagggactg gcggcattcc tcatggacag gcatattata 14520 gtacctaggg cagctcatga aatcctggat catagtgtca caggggcaag agagtctatt 14580 gtacctaggg cagctcatga aatcctggat catagtgtca caggggcaag agagtctatt 14580 gcaggcatgc tggataccac aaaaggcttg attcgagcca gcatgaggaa gggggggtta 14640 gcaggcatgc tggataccac aaaaggcttg attcgagcca gcatgaggaa gggggggtta 14640 acctctcgag tgataaccag attgtccaat tatgactatg aacaattcag agcagggatg 14700 acctctcgag tgataaccag attgtccaat tatgactatg aacaattcag agcagggatg 14700 gtgctattga caggaagaaa gagaaatgtc ctcattgaca aagagtcatg ttcagtgcag 14760 gtgctattga caggaagaaa gagaaatgtc ctcattgaca aagagtcatg ttcagtgcag 14760 ctggcgagag ctctaagaag ccatatgtgg gcgaggctag ctcgaggacg gcctatttac 14820 ctggcgagag ctctaagaag ccatatgtgg gcgaggctag ctcgaggacg gcctatttac 14820 ggccttgagg tccctgatgt actagaatct atgcgaggcc accttattcg gcgtcatgag 14880 ggccttgagg tccctgatgt actagaatct atgcgaggcc accttattcg gcgtcatgag 14880 acatgtgtca tctgcgagtg tggatcagtc aactacggat ggttttttgt cccctcgggt 14940 acatgtgtca tctgcgagtg tggatcagtc aactacggat ggttttttgt cccctcgggt 14940 tgccaactgg atgatattga caaggaaaca tcatccttga gagtcccata tattggttct 15000 tgccaactgg atgatattga caaggaaaca tcatccttga gagtcccata tattggttct 15000 accactgatg agagaacaga catgaagctt gccttcgtaa gagccccaag tcgatccttg 15060 accactgatg agagaacaga catgaagctt gccttcgtaa gagccccaag tcgatccttg 15060 cgatctgctg ttagaatagc aacagtgtac tcatgggctt acggtgatga tgatagctct 15120 cgatctgctg ttagaatagc aacagtgtac tcatgggctt acggtgatga tgatagctct 15120 tggaacgaag cctggttgtt ggctaggcaa agggccaatg tgagcctgga ggagctaagg 15180 tggaacgaag cctggttgtt ggctaggcaa agggccaatg tgagcctgga ggagctaagg 15180 gtgatcactc ccatctcaac ttcgactaat ttagcgcata ggttgaggga tcgtagcact 15240 gtgatcactc ccatctcaac ttcgactaat ttagcgcata ggttgaggga tcgtagcact 15240 caagtgaaat actcaggtac atcccttgtc cgagtggcga ggtataccac aatctccaac 15300 caagtgaaat actcaggtac atcccttgtc cgagtggcga ggtataccac aatctccaac 15300 gacaatctct catttgtcat atcagataag aaggttgata ctaactttat ataccaacaa 15360 ggaatgcttc tagggttggg tgttttagaa acattgtttc gactcgagaa agataccgga 15420 tcatctaaca cggtattaca tcttcacgtc gaaacagatt gttgcgtgat cccgatgata 15480 gatcatccca ggatacccag ctcccgcaag ctagagctga gggcagagct atgtaccaac 15540 ccattgatat atgataatgc acctttaatt gacagagatg caacaaggct atacacccag 15600 agccatagga ggcaccttgt ggaatttgtt acatggtcca caccccaact atatcacatt 15660 ttagctaagt ccacagcact atctatgatt gacctggtaa caaaatttga gaaggaccat 15720 atgaatgaaa tttcagctct cataggggat gacgatatca atagtttcat aactgagttt 15780 ctgctcatag agccaagatt attcactatc tacttgggcc agtgtgcggc catcaattgg 15840 gcatttgatg tacattatca tagaccatca gggaaatatc agatgggtga gctgttgtca 15900 tcgttccttt ctagaatgag caaaggagtg tttaaggtgc ttgtcaatgc tctaagccac 15960 ccaaagatct acaagaaatt ctggcattgt ggtattatag agcctatcca tggtccttca 16020 cttgatgctc aaaacttgca cacaactgtg tgcaacatgg tttacacatg ctatatgacc 16080 cttgatgctc aaaacttgca cacaactgtg tgcaacatgg tttacacatg ctatatgacc 16080 tacctcgacc tgttgttgaa tgaagagtta gaagagttca catttctctt gtgtgaaagc 16140 tacctcgacc tgttgttgaa tgaagagtta gaagagttca catttctctt gtgtgaaagc 16140 gacgaggatg tagtaccgga cagattcgac aacatccagg caaaacactt atgtgttctg 16200 gacgaggatg tagtaccgga cagattcgac aacatccagg caaaacactt atgtgttctg 16200 gcagatttgt actgtcaacc agggacctgc ccaccaattc gaggtctaag accggtagag 16260 gcagatttgt actgtcaacc agggacctgc ccaccaattc gaggtctaag accggtagag 16260 aaatgtgcag ttctaaccga ccatatcaag gcagaggcta tgttatctcc agcaggatct 16320 aaatgtgcag ttctaaccga ccatatcaag gcagaggcta tgttatctcc agcaggatct 16320 tcgtggaaca taaatccaat tattgtagac cattactcat gctctctgac ttatctccgg 16380 tcgtggaaca taaatccaat tattgtagac cattactcat gctctctgac ttatctccgg 16380 cgaggatcga tcaaacagat aagattgaga gttgatccag gattcatttt cgacgccctc 16440 cgaggatcga tcaaacagat aagattgaga gttgatccag gattcatttt cgacgccctc 16440 gctgaggtaa atgtcagtca gccaaagatc ggcagcaaca acatctcaaa tatgagcatc 16500 gctgaggtaa atgtcagtca gccaaagatc ggcagcaaca acatctcaaa tatgagcatc 16500 aaggctttca gacccccaca cgatgatgtt gcaaaattgc tcaaagatat caacacaagc 16560 aaggctttca gacccccaca cgatgatgtt gcaaaattgc tcaaagatat caacacaagc 16560 aagcacaatc ttcccatttc agggggcaat ctcgccaatt atgaaatcca tgctttccgc 16620 aagcacaatc ttcccatttc agggggcaat ctcgccaatt atgaaatcca tgctttccgc 16620 agaatcgggt tgaactcatc tgcttgctac aaagctgttg agatatcaac attaattagg 16680 agaatcgggt tgaactcatc tgcttgctac aaagctgttg agatatcaac attaattagg 16680 agatgccttg agccagggga ggacggcttg ttcttgggtg agggatcggg ttctatgttg 16740 atcacttata aagagatact taaactaaac aagtgcttct ataatagtgg ggtttccgcc 16800 aattctagat ctggtcaaag ggaattagca ccctatccct ccgaagttgg ccttgtcgaa 16860 cacagaatgg gagtaggtaa tattgtcaaa gtgctcttta acgggaggcc cgaagtcacg 16920 tgggtaggca gtgtagattg cttcaatttc atagttagta atatccctac ctctagtgtg 16980 gggtttatcc attcagatat agagaccttg cctgacaaag atactataga gaagctagag 17040 gaattggcag ccatcttatc gatggctctg ctcctgggca aaataggatc aatactggtg 17100 attaagctta tgcctttcag cggggatttt gttcagggat ttataagtta tgtagggtct 17160 cattatagag aagtgaacct tgtataccct agatacagca acttcatctc tactgaatct 17220 tatttggtta tgacagatct caaggctaac cggctaatga atcctgaaaa gattaagcag 17280 cagataattg aatcatctgt gaggacttca cctggactta taggtcacat cctatccatt 17340 aagcaactaa gctgcataca agcaattgtg ggagacgcag ttagtagagg tgatatcaat 17400 cctactctga aaaaacttac acctatagag caggtgctga tcaattgcgg gttggcaatt 17460 cctactctga aaaaacttac acctatagag caggtgctga tcaattgcgg gttggcaatt 17460 aacggaccta agctgtgcaa agaattgatc caccatgatg ttgcctcagg gcaagatgga 17520 aacggaccta agctgtgcaa agaattgatc caccatgatg ttgcctcagg gcaagatgga 17520 ttgcttaatt ctatactcat cctctacagg gagttggcaa gattcaaaga caaccaaaga 17580 ttgcttaatt ctatactcat cctctacagg gagttggcaa gattcaaaga caaccaaaga 17580 agtcaacaag ggatgttcca cgcttacccc gtattggtaa gtagcaggca acgagaactt 17640 agtcaacaag ggatgttcca cgcttacccc gtattggtaa gtagcaggca acgagaactt 17640 atatctagga tcacccgcaa attctggggg cacattcttc tttactccgg gaacaaaaag 17700 atatctagga tcacccgcaa attctggggg cacattcttc tttactccgg gaacaaaaag 17700 ttgataaata agtttatcca gaatctcaag tccggctatc tgatactaga cttacaccag 17760 ttgataaata agtttatcca gaatctcaag tccggctatc tgatactaga cttacaccag 17760 aatatcttcg ttaagaatct atccaagtca gagaaacaga ttattatgac ggggggtttg 17820 aatatcttcg ttaagaatct atccaagtca gagaaacaga ttattatgac ggggggtttg 17820 aaacgtgagt gggtttttaa ggtaacagtc aaggagacca aagaatggta taagttagtc 17880 aaacgtgagt gggtttttaa ggtaacagtc aaggagacca aagaatggta taagttagtc 17880 ggatacagtg ccctgattaa ggactaattg gttgaactcc ggaaccctaa tcctgcccta 17940 ggatacagtg ccctgattaa ggactaattg gttgaactcc ggaaccctaa tcctgcccta 17940 ggtggttagg cattatttgc aatatattaa agaaaacttt gaaaatacga agtttctatt 18000 ggtggttagg cattatttgc aatatattaa agaaaacttt gaaaatacga agtttctatt 18000 cccagctttg tctggtggcc ggcatggtcc cagcctcctc gctggcgccg gctgggcaac 18060 cccagctttg tctggtggcc ggcatggtcc cagcctcctc gctggcgccg gctgggcaac 18060 attccgaggg gaccgtcccc tcggtaatgg cgaatgggac gcggccgatc cggctgctaa 18120 caaagcccga aaggaagctg agttggctgc tgccaccgct gagcaataac tagcataacc 18180 ccttggggcc tctaaacggg tcttgagggg ttttttgctg aaaggaggaa ctatatccgg 18240 atgcggccgc gggccctatg gtacccagct tttgttccct ttagtgaggg ttaattccga 18300 gcttggcgta atcatggtca tagctgtttc ctgtgtgaaa ttgttatccg ctcacaattc 18360 cacacaacat aggagccgga agcataaagt gtaaagcctg gggtgcctaa tgagtgaggt 18420 aactcacatt aattgcgttg cgctcactgc ccgctttcca gtcgggaaac ctgtcgtgcc 18480 agctgcatta atgaatcggc caacgcgcgg ggagaggcgg tttgcgtatt gggcgctctt 18540 ccgcttcctc gctcactgac tcgctgcgct cggtcgttcg gctgcggcga gcggtatcag 18600 ctcactcaaa ggcggtaata cggttatcca cagaatcagg ggataacgca ggaaagaaca 18660 tgtgagcaaa aggccagcaa aaggccagga accgtaaaaa ggccgcgttg ctggcgtttt 18720 tccataggct cggcccccct gacgagcatc acaaaaatcg acgctcaagt cagaggtggc 18780 gaaacccgac aggactataa agataccagg cgttcccccc tggaagctcc ctcgtgcgct 18840 gaaacccgac aggactataa agataccagg cgttcccccc tggaagctcc ctcgtgcgct 18840 ctcctgttcc gaccctgccg cttaccggat acctgtccgc ctttctccct tcgggaagcg 18900 ctcctgttcc gaccctgccg cttaccggat acctgtccgc ctttctccct tcgggaagcg 18900 tggcgctttc tcaatgctca cgctgtaggt atctcagttc ggtgtaggtc gttcgctcca 18960 tggcgctttc tcaatgctca cgctgtaggt atctcagttc ggtgtaggtc gttcgctcca 18960 agctgggctg tgtgcacgaa ccccccgttc agcccgaccg ctgcgcctta tccggtaact 19020 agctgggctg tgtgcacgaa ccccccgttc agcccgaccg ctgcgcctta tccggtaact 19020 atcgtcttga gtccaacccg gtaagacacg acttatcgcc actggcagca gccactggta 19080 atcgtcttga gtccaacccg gtaagacacg acttatcgcc actggcagca gccactggta 19080 acaggattag cagagcgagg tatgtaggcg gtgctacaga gttcttgaag tggtggccta 19140 acaggattag cagagcgagg tatgtaggcg gtgctacaga gttcttgaag tggtggccta 19140 actacggcta cactagaagg acagtatttg gtatctgcgc tctgctgaag ccagttacct 19200 actacggcta cactagaagg acagtatttg gtatctgcgc tctgctgaag ccagttacct 19200 tcggaaaaag agttggtagc tcttgatccg gcaaacaaac caccgctggt agcggtggtt 19260 tcggaaaaag agttggtagc tcttgatccg gcaaacaaac caccgctggt agcggtggtt 19260 tttttgtttg caagcagcag attacgcgca gaaaaaaagg atctcaagaa gatcctttga 19320 tttttgtttg caagcagcag attacgcgca gaaaaaaagg atctcaagaa gatcctttga 19320 tcttttctac ggggtctgac gctcagtgga acgaaaactc acgttaaggg attttggtca 19380 tcttttctac ggggtctgac gctcagtgga acgaaaactc acgttaaggg attttggtca 19380 tgagattatc aaaaaggatc ttcacctaga tccttttaaa ttaaaaatga agttttaaat 19440 tgagattatc aaaaaggatc ttcacctaga tccttttaaa ttaaaaatga agttttaaat 19440 caatctaaag tatatatgag taaacttggt ctgacagtta ccaatgctta atcagtgagg 19500 cacctatctc agcgatctgt ctatttcgtt catccatagt tgcctgactg cccgtcgtgt 19560 agataactac gatacgggag ggcttaccat ctggccccag tgctgcaatg ataccgcgag 19620 acccacgctc accggctcca gatttatcag caataaacca gccagccgga agggccgagc 19680 gcagaagtgg tcctgcaact ttatccgcct ccatccagtc tattaattgt tgccgggaag 19740 ctagagtaag tagttcgcca gttaatagtt tgcgcaacgt tgttgccatt gctacaggca 19800 tcgtggtgtc acgctcgtcg tttggtatgg cttcattcag ctccggttcc caacgatcaa 19860 ggcgagttac atgatccccc atgttgtgaa aaaaagcggt tagctccttc ggtcctccga 19920 tcgttgtcag aagtaagttg gccgcagtgt tatcactcat gcttatggca gcactgcata 19980 attctcttac tgtcatgcca tccgtaagat gcttttctgt gactggtgag tactcaacca 20040 agtcattctg agaatagtgt atgcggcgac cgagttgctc ttgcccggcg tcaatacggg 20100 ataataccgc gccacatagc agaactttaa aagtgctcat cattggaaaa cgttcttcgg 20160 ggcgaaaact ctcaaggatc ttaccgctgt tgagatccag ttcgatgtaa cccactcgtg 20220 cacccaactg atcttcagca tcttttactt tcaccagcgt ttctgggtga gcaaaaacag 20280 gaaggcaaaa tgccgcaaaa aagggaataa gggcgacacg gaaatgttga atactcatac 20340 tcttcctttt tcaatattat tgaagcattt atcagggtta ttgtctcatg agcggataca 20400 tatttgaatg tatttagaaa aataaacaaa taggggttcc gcgcacattt ccccgaaaag 20460 tgccacctga aattgtaaac gttaatattt tgttaaaatt cgcgttaaat ttttgttaaa 20520 tcagctcatt ttttaaccaa taggccgaaa tcggcaaaat cccttataaa tcaaaagaat 20580 agaccgagat agggttgagt gttgttccag tttggaacaa gagtccacta ttaaagaacg 20640 tggactccaa cgtcaaaggg cgaaaaaccg tctatcaggg cgatggccca ctacgtgaac 20700 catcacccta atcaagtttt ttggggtcga ggtgccgtaa agcactaaat cggaacccta 20760 aagggagccc ccgatttaga gcttgacggg gaaagccggc gaacgtggcg agaaaggaag 20820 ggaagaaagc gaaaggagcg ggcgctaggg cgctggcaag tgtagcggtc acgctgcgcg 20880 taaccaccac acccgccgcg cttaatgcgc cgctacaggg cgcgtcccat tcgccattca 20940 ggctgcgcaa ctgttgggaa gggcgatcgg tgcgggcctc ttcgctatta cgccagccac 21000 cgcggtg 21007 <210> 13 <211> 22861 <212> DNA <213> Artificial Sequence <220> <223> Plasmid MeV-Z-NP-GPC <400> 13 gcggccgcta atacgactca ctatagggcc aactttgttt ggtctgatga gtccgtgagg 60 acgaaacccg gagtcccggg tcaccaaaca aagttgggta aggatagttc aatcaatgat 120 catcttctag tgcacttagg attcaagatc ctattatcag ggacaagagc aggattaggg 180 atatccgaga cgcgtacgat gggcaataag caggcaaagg cacccgaaag caaggattca 240 cctagagcat cactgattcc cgacgcaact catctggggc cacagttctg caaatcctgt 300 tggttcgaga acaaaggcct ggtggagtgc aataaccact acctgtgcct gaactgtctg 360 acactgctgc tgagtgtgag caacagatgc ccaatctgca agatgcctct gccaacaaag 420 ctgaggcctt ctgctgcacc caccgcacca ccaactggag ccgcagacag cattagaccc 480 cccccatact caccataagc gcgcagcgct tagacgtctc gcgatcgatt agtgcgagag 540 gccgagggcc agaacaacat ccgcctacca tccatcattg ttataaaaaa cttaggattc 600 aagatcctat tatcagggac aagagcagga ttagggatat ccgagatggc cacactttta 660 aggagcttag cattgttcaa aagaaacaag gacaaaccac ccattacatc aggatccggt 720 ggagccatca gaggaatcaa acacattatt atagtaccaa tccctggaga ttcctcaatt 780 accactcgat ccagacttct ggaccggttg gtgaggttaa ttggaaaccc ggatgtgagc 840 gggcccaaac taacaggggc actaataggt atattatcct tatttgtgga gtctccaggt 900 caattgattc agaggatcac cgatgaccct gacgttagca taaggctgtt agaggttgtc 960 cagagtgacc agtcacaatc tggccttacc ttcgcatcaa gaggtaccaa catggaggat 1020 gaggcggacc aatacttttc acatgatgat ccaattagta gtgatcaatc caggttcgga 1080 tggttcggga acaaggaaat ctcagatatt gaagtgcaag accctgaggg attcaacatg 1140 attctgggta ccatcctagc ccaaatttgg gtcttgctcg caaaggcggt tacggcccca 1200 gacacggcag ctgattcgga gctaagaagg tggataaagt acacccaaca aagaagggta 1260 gttggtgaat ttagattgga gagaaaatgg ttggatgtgg tgaggaacag gattgccgag 1320 gacctctcct tacgccgatt catggtcgct ctaatcctgg atatcaagag aacacccgga 1380 aacaaaccca ggattgctga aatgatatgt gacattgata catatatcgt agaggcagga 1440 ttagccagtt ttatcctgac tattaagttt gggatagaaa ctatgtatcc tgctcttgga 1500 ctgcatgaat ttgctggtga gttatccaca cttgagtcct tgatgaacct ttaccagcaa 1560 atgggggaaa ctgcacccta catggtaatc ctggagaact caattcagaa caagttcagt 1620 gcaggatcat accctctgct ctggagctat gccatgggag taggagtgga acttgaaaac 1680 tccatgggag gtttgaactt tggccgatct tactttgatc cagcatattt tagattaggg 1740 caagagatgg taaggaggtc agctggaaag gtcagttcca cattggcatc tgaactcggt 1800 atcactgccg aggatgcaag gcttgtttca gagattgcaa tgcatactac tgaggacaag 1860 atcagtagag cggttggacc cagacaagcc caagtatcat ttctacacgg tgatcaaagt 1920 gagaatgagc taccgagatt ggggggcaag gaagatagga gggtcaaaca gagtcgagga 1980 gaagccaggg agagctacag agaaaccggg cccagcagag caagtgatgc gagagctgcc 2040 catcttccaa ccggcacacc cctagacatt gacactgcaa cggagtccag ccaagatccg 2100 caggacagtc gaaggtcagc tgacgccctg cttaggctgc aagccatggc aggaatctcg 2160 gaagaacaag gctcagacac ggacacccct atagtgtaca atgacagaaa tcttctagac 2220 taggtgcgag aggccgaggg ccagaacaac atccgcctac catccatcat tgttataaaa 2280 aacttaggaa ccaggtccac acagccgcca gcccatcaac catccactcc cacgattgga 2340 gccaatggca gaagagcagg cacgccatgt caaaaacgga ctggaatgca tccgggctct 2400 caaggccgag cccatcggct cactggccat cgaggaagct atggcagcat ggtcagaaat 2460 atcagacaac ccaggacagg agcgagccac ctgcagggaa gagaaggcag gcagttcggg 2520 tctcagcaaa ccatgcctct cagcaattgg atcaactgaa ggcggtgcac ctcgcatccg 2580 cggtcaggga cctggagaga gcgatgacga cgctgaaact ttgggaatcc ccccaagaaa 2640 tctccaggca tcaagcactg ggttacagtg ttattacgtt tatgatcaca gcggtgaagc 2700 ggttaaggga atccaagatg ctgactctat catggttcaa tcaggccttg atggtgatag 2760 caccctctca ggaggagaca atgaatctga aaacagcgat gtggatattg gcgaacctga 2820 taccgaggga tatgctatca ctgaccgggg atctgctccc atctctatgg ggttcagggc 2880 ttctgatgtt gaaactgcag aaggagggga gatccacgag ctcctgagac tccaatccag 2940 aggcaacaac tttccgaagc ttgggaaaac tctcaatgtt cctccgcccc cggaccccgg 3000 tagggccagc acttccggga cacccattaa aaagggcaca gacgcgagat tagcctcatt 3060 tggaacggag atcgcgtctt tattgacagg tggtgcaacc caatgtgctc gaaagtcacc 3120 ctcggaacca tcagggccag gtgcacctgc ggggaatgtc cccgagtgtg tgagcaatgc 3180 cgcactgata caggagtgga cacccgaatc tggtaccaca atctccccga gatcccagaa 3240 taatgaagaa gggggagact attatgatga tgagctgttc tctgatgtcc aagatattaa 3300 aacagccttg gccaaaatac acgaggataa tcagaagata atctccaagc tagaatcact 3360 gctgttattg aagggagaag ttgagtcaat taagaagcag atcaacaggc aaaatatcag 3420 catatccacc ctggaaggac acctctcaag catcatgatc gccattcctg gacttgggaa 3480 ggatcccaac gaccccactg cagatgtcga aatcaatccc gacttgaaac ccatcatagg 3540 cagagattca ggccgagcac tggccgaagt tctcaagaaa cccgttgcca gccgacaact 3600 ccaaggaatg acaaatggac ggaccagttc cagaggacag ctgctgaagg aatttcagct 3660 aaagccgatc gggaaaaaga tgagctcagc cgtcgggttt gttcctgaca ccggccctgc 3720 atcacgcagt gtaatccgct ccattataaa atccagccgg ctagaggagg atcggaagcg 3780 ttacctgatg actctccttg atgatatcaa aggagccaat gatcttgcca agttccacca 3840 gatgctgatg aagataataa tgaagtagct acagctcaac ttacctgcca accccatgcc 3900 agtcgaccca actagcctac cctccatcat tgttataaaa aacttaggaa ccaggtccac 3960 acagccgcca gcccatcaac gcgtacgatg agtgccagca aagaaatcaa gagcttcctg 4020 tggacccaga gtctgcggag ggaactgagc ggatactgta gcaacatcaa actgcaggtg 4080 gtcaaggacg ctcaggcact gctgcatggg ctggacttct ccgaggtgtc taatgtgcag 4140 cggctgatgc ggaaagaacg gagggacgat aatgacctga agcgactgcg cgacctgaac 4200 caggcagtga acaatctggt cgagctgaag agcacccagc agaaatcaat cctgcgggtc 4260 gggacactga catctgacga cctgctgatc ctggctgcag acctggagaa gctgaaatcg 4320 aaagtgatcc gcaccgaaag gccactgtcc gccggggtct acatgggcaa tctgtcttcc 4380 cagcagctgg accagaggcg ggctctgctg aacatgattg ggatgtccgg aggaaatcag 4440 ggagctagag ccgggaggga cggagtcgtg cgggtctggg acgtgaagaa tgccgaactg 4500 ctgaacaacc agttcgggac catgccaagt ctgacactgg catgcctgac taaacagggc 4560 caggtggatc tgaatgatgc agtccaggct ctgaccgacc tgggcctgat ctacaccgcc 4620 aagtacccca atactagcga cctggataga ctgacccaga gccaccccat cctgaacatg 4680 atcgacacta agaagtcctc actgaacatc agtggctata atttctccct gggggcagca 4740 gtcaaggctg gcgcatgcat gctggacggc gggaatatgc tggaaaccat caaagtgtct 4800 ccccagacca tggatggcat cctgaaatct attctgaaag tcaagaaggc cctgggaatg 4860 tttatttcag acacccccgg cgagaggaat ccatatgaga acattctgta taagatttgc 4920 ctgagtggcg acgggtggcc atacattgca agccggacat caattaccgg aagagcttgg 4980 gagaatacag tcgtggacct ggaaagcgac ggcaagcccc agaaggccga ctcaaacaac 5040 tcctcaaaga gtctgcagtc agctggcttc acagcagggc tgacttactc ccagctgatg 5100 acactgaagg acgcaatgct gcagctggac ccaaacgcta agacatggat ggacatcgag 5160 ggacggccag aagatccagt ggaaatcgca ctgtatcagc catcatccgg atgctatatc 5220 catttcttcc gggaaccaac tgatctgaag cagttcaagc aggatgcaaa gtactcccac 5280 ggaatcgatg tcaccgatct gttcgcaacc cagccaggac tgacatcagc cgtcatcgat 5340 gccctgccta ggaacatggt cattacttgc cagggctccg acgatattag gaagctgctg 5400 gagagccagg gacggaagga tatcaaactg atcgatattg ccctgtctaa gactgatagc 5460 cggaaatatg agaatgcagt ctgggatcag tacaaggacc tgtgccatat gcataccgga 5520 gtggtcgtcg agaagaagaa gaggggcgga aaggaagaga tcacacccca ctgtgccctg 5580 atggattgca tcatgttcga cgcagccgtg tccgggggcc tgaacacctc agtcctgagg 5640 gctgtcctgc caagagatat ggtgtttaga acttcaaccc caagagtcgt cctgtaattc 5700 gaactacagc tcaacttacc tgccaacccc atgccagtcg acccaactag tacaacctaa 5760 atccattata aaaaacttag gaaccaggtc cacacagccg ccagcccatc aaccatccac 5820 tcccacgatt ggaggccggc catgggccag attgtcacat tctttcagga agtgccacac 5880 gtcattgagg aggtcatgaa catcgtgctg attgctctgt cagtgctggc agtgctgaaa 5940 ggactgtaca acttcgctac ctgtggactg gtgggactgg tcacattcct gctgctgtgc 6000 ggcagaagtt gcactacctc actgtacaaa ggagtgtacg agctgcagac tctggaactg 6060 aacatggaga cactgaatat gacaatgcct ctgagctgca ccaagaataa tagccaccac 6120 tatatcatgg tcgggaacga aaccggcctg gaactgaccc tgacaaacac cagcatcatt 6180 aaccacaagt tctgcaatct gagcgacgct cacaagaaga acctgtatga ccacgctctg 6240 atgtccatca tcagtacctt tcacctgtcc atccccaatt tcaaccagta cgaggcaatg 6300 tcatgcgact tcaacggggg caagatcagt gtccagtaca acctgagcca ctcctacgcc 6360 ggcgacgcag ccaaccactg cggaactgtc gccaatggcg tgctgcagac attcatgagg 6420 atggcatggg ggggatctta catcgcactg gatagcggca ggggcaattg ggattgcatc 6480 atgacttcct atcagtatct gattatccag aatactacat gggaggatca ttgccagttc 6540 agtcggccca gccctattgg atatctgggg ctgctgtcac agagaacacg ggatatctat 6600 atttcaagac gcctgctggg cacattcact tggacactgt cagacagtga gggcaaggat 6660 actccagggg gctactgcct gacacgatgg atgctgatcg aagcagagct gaaatgcttc 6720 ggcaataccg cagtggccaa gtgcaacgag aaacacgacg aggagttctg cgacatgctg 6780 aggctgttcg acttcaacaa acaggctatc cagagactga aggcagaagc ccagatgtca 6840 atccagctga tcaacaaggc agtgaacgcc ctgatcaacg accagctgat catgaagaac 6900 cacctgagag acattatggg catcccctac tgtaattaca gcaagtattg gtacctgaac 6960 cacactacaa ccgggagaac atccctgccc aagtgctggc tggtcagcaa tgggagttat 7020 ctgaatgaaa cccatttcag cgacgatatc gaacagcagg ctgacaacat gatcacagag 7080 atgctgcaga aagagtacat ggaaagacag ggcaagacac cactgggact ggtcgatctg 7140 ttcgtcttct ccactagctt ctatctgatt tccatcttcc tgcacctggt gaagatcccc 7200 actcataggc acattgtcgg caagagttgc cctaaacccc ataggctgaa tcacatgggg 7260 atttgtagtt gcggcctgta taagcagcct ggcgtgcctg tgaagtggaa gagatgagcg 7320 cgcagcgctt agacgtctcg cgatcgatac tagtacaacc taaatccatt ataaaaaact 7380 taggagcaaa gtgattgcct cccaaggtcc acaatgacag agacctacga cttcgacaag 7440 tcggcatggg acatcaaagg gtcgatcgct ccgatacaac ccaccaccta cagtgatggc 7500 aggctggtgc cccaggtcag agtcatagat cctggtctag gcgacaggaa ggatgaatgc 7560 tttatgtaca tgtttctgct gggggttgtt gaggacagcg attccctagg gcctccaatc 7620 gggcgagcat ttgggttcct gcccttaggt gttggcagat ccacagcaaa gcccgaaaaa 7680 ctcctcaaag aggccactga gcttgacata gttgttagac gtacagcagg gctcaatgaa 7740 aaactggtgt tctacaacaa caccccacta actctcctca caccttggag aaaggtccta 7800 acaacaggga gtgtcttcaa cgcaaaccaa gtgtgcaatg cggttaatct gataccgctc 7860 gataccccgc agaggttccg tgttgtttat atgagcatca cccgtctttc ggataacggg 7920 tattacaccg ttcctagaag aatgctggaa ttcagatcgg tcaatgcagt ggccttcaac 7980 ctgctggtga cccttaggat tgacaaggcg ataggccctg ggaagatcat cgacaataca 8040 gagcaacttc ctgaggcaac atttatggtc cacatcggga acttcaggag aaagaagagt 8100 gaagtctact ctgccgatta ttgcaaaatg aaaatcgaaa agatgggcct ggtttttgca 8160 cttggtggga tagggggcac cagtcttcac attagaagca caggcaaaat gagcaagact 8220 ctccatgcac aactcgggtt caagaagacc ttatgttacc cgctgatgga tatcaatgaa 8280 gaccttaatc gattactctg gaggagcaga tgcaagatag taagaatcca ggcagttttg 8340 cagccatcag ttcctcaaga attccgcatt tacgacgacg tgatcataaa tgatgaccaa 8400 ggactattca aagttctgta gaccgtagtg cccagcaatg cccgaaaacg acccccctca 8460 caatgacagc cagaaggccc ggacaaaaaa gccccctccg aaagactcca cggaccaagc 8520 gagaggccag ccagcagccg acggcaagcg cgaacaccag gcggccccag cacagaacag 8580 ccctgacaca aggccaccac cagccacccc aatctgcatc ctcctcgtgg gacccccgag 8640 gaccaacccc caaggctgcc cccgatccaa accaccaacc gcatccccac cacccccggg 8700 aaagaaaccc ccagcaattg gaaggcccct ccccctcttc ctcaacacaa gaactccaca 8760 accgaaccgc acaagcgacc gaggtgaccc aaccgcaggc atccgactcc ctagacagat 8820 cctctctccc cggcaaacta aacaaaactt agggccaagg aacatacaca cccaacagaa 8880 cccagacccc ggcccacggc gccgcgcccc caacccccga caaccagagg gagcccccaa 8940 ccaatcccgc cggctccccc ggtgcccaca ggcagggaca ccaacccccg aacagaccca 9000 gcacccaacc atcgacaatc caagacgggg gggccccccc aaaaaaaggc ccccaggggc 9060 cgacagccag caccgcgagg aagcccaccc accccacaca cgaccacggc aaccaaacca 9120 gaacccagac caccctgggc caccagctcc cagactcggc catcaccccg cagaaaggaa 9180 aggccacaac ccgcgcaccc cagccccgat ccggcgggga gccacccaac ccgaaccagc 9240 acccaagagc gatccccgaa ggacccccga accgcaaagg acatcagtat cccacagcct 9300 ctccaagtcc cccggtctcc tcctcttctc gaagggacca aaagatcaat ccaccacacc 9360 cgacgacact caactcccca cccctaaagg agacaccggg aatcccagaa tcaagactca 9420 tccaatgtcc atcatgggtc tcaaggtgaa cgtctctgcc atattcatgg cagtactgtt 9480 aactctccaa acacccaccg gtcaaatcca ttggggcaat ctctctaaga taggggtggt 9540 aggaatagga agtgcaagct acaaagttat gactcgttcc agccatcaat cattagtcat 9600 aaaattaatg cccaatataa ctctcctcaa taactgcacg agggtagaga ttgcagaata 9660 caggagacta ctgagaacag ttttggaacc aattagagat gcacttaatg caatgaccca 9720 gaatataaga ccggttcaga gtgtagcttc aagtaggaga cacaagagat ttgcgggagt 9780 agtcctggca ggtgcggccc taggcgttgc cacagctgct cagataacag ccggcattgc 9840 acttcaccag tccatgctga actctcaagc catcgacaat ctgagagcga gcctggaaac 9900 tactaatcag gcaattgaga caatcagaca agcagggcag gagatgatat tggctgttca 9960 gggtgtccaa gactacatca ataatgagct gataccgtct atgaaccaac tatcttgtga 10020 tttaatcggc cagaagctcg ggctcaaatt gctcagatac tatacagaaa tcctgtcatt 10080 atttggcccc agtttacggg accccatatc tgcggagata tctatccagg ctttgagcta 10140 tgcgcttgga ggagacatca ataaggtgtt agaaaagctc ggatacagtg gaggtgattt 10200 actgggcatc ttagagagcg gaggaataaa ggcccggata actcacgtcg acacagagtc 10260 ctacttcatt gtcctcagta tagcctatcc gacgctgtcc gagattaagg gggtgattgt 10320 ccaccggcta gagggggtct cgtacaacat aggctctcaa gagtggtata ccactgtgcc 10380 caagtatgtt gcaacccaag ggtaccttat ctcgaatttt gatgagtcat cgtgtacttt 10440 catgccagag gggactgtgt gcagccaaaa tgccttgtac ccgatgagtc ctctgctcca 10500 catgccagag gggactgtgt gcagccaaaa tgccttgtac ccgatgagtc ctctgctcca 10500 agaatgcctc cgggggtaca ccaagtcctg tgctcgtaca ctcgtatccg ggtcttttgg 10560 agaatgcctc cgggggtaca ccaagtcctg tgctcgtaca ctcgtatccg ggtcttttgg 10560 gaaccggttc attttatcac aagggaacct aatagccaat tgtgcatcaa tcctttgcaa 10620 gaaccggttc attttatcac aagggaacct aatagccaat tgtgcatcaa tcctttgcaa 10620 gtgttacaca acaggaacga tcattaatca agaccctgac aagatcctaa catacattgc 10680 gtgttacaca acaggaacga tcattaatca agaccctgac aagatcctaa catacattgc 10680 tgccgatcac tgcccggtag tcgaggtgaa cggcgtgacc atccaagtcg ggagcaggag 10740 tgccgatcac tgcccggtag tcgaggtgaa cggcgtgacc atccaagtcg ggagcaggag 10740 gtatccagac gctgtgtact tgcacagaat tgacctcggt cctcccatat cattggagag 10800 gtatccagac gctgtgtact tgcacagaat tgacctcggt cctcccatat cattggagag 10800 gttggacgta gggacaaatc tggggaatgc aattgctaag ttggaggatg ccaaggaatt 10860 gttggacgta gggacaaatc tggggaatgc aattgctaag ttggaggatg ccaaggaatt 10860 gttggagtca tcggaccaga tattgaggag tatgaaaggt ttatcgagca ctagcatagt 10920 gttggagtca tcggaccaga tattgaggag tatgaaaggt ttatcgagca ctagcatagt 10920 ctacatcctg attgcagtgt gtcttggagg gttgataggg atccccgctt taatatgttg 10980 ctacatcctg attgcagtgt gtcttggagg gttgataggg atccccgctt taatatgttg 10980 ctgcaggggg cgttgtaaca aaaagggaga acaagttggt atgtcaagac caggcctaaa 11040 ctgcaggggg cgttgtaaca aaaagggaga acaagttggt atgtcaagac caggcctaaa 11040 gcctgatctt acgggaacat caaaatccta tgtaaggtcg ctctgatcct ctacaactct 11100 gcctgatctt acgggaacat caaaatccta tgtaaggtcg ctctgatcct ctacaactct 11100 tgaaacacaa atgtcccaca agtctcctct tcgtcatcaa gcaaccaccg cacccagcat 11160 caagcccacc tgaaattatc tccggcttcc ctctggccga acaatatcgg tagttaatca 11220 aaacttaggg tgcaagatca tccacaatgt caccacaacg agaccggata aatgccttct 11280 acaaagataa cccccatccc aagggaagta ggatagtcat taacagagaa catcttatga 11340 ttgatagacc ttatgttttg ctggctgttc tgtttgtcat gtttctgagc ttgatcgggt 11400 tgctagccat tgcaggcatt agacttcatc gggcagccat ctacaccgca gagatccata 11460 aaagcctcag caccaatcta gatgtaacta actcaatcga gcatcaggtc aaggacgtgc 11520 tgacaccact cttcaaaatc atcggtgatg aagtgggcct gaggacacct cagagattca 11580 ctgacctagt gaaattaatc tctgacaaga ttaaattcct taatccggat agggagtacg 11640 acttcagaga tctcacttgg tgtatcaacc cgccagagag aatcaaattg gattatgatc 11700 aatactgtgc agatgtggct gctgaagagc tcatgaatgc attggtgaac tcaactctac 11760 tggagaccag aacaaccaat cagttcctag ctgtctcaaa gggaaactgc tcagggccca 11820 ctacaatcag aggtcaattc tcaaacatgt cgctgtccct gttagacttg tatttaggtc 11880 gaggttacaa tgtgtcatct atagtcacta tgacatccca gggaatgtat gggggaactt 11940 acctagtgga aaagcctaat ctgagcagca aaaggtcaga gttgtcacaa ctgagcatgt 12000 accgagtgtt tgaagtaggt gttatcagaa atccgggttt gggggctccg gtgttccata 12060 tgacaaacta tcttgagcaa ccagtcagta atgatctcag caactgtatg gtggctttgg 12120 gggagctcaa actcgcagcc ctttgtcacg gggaagattc tatcacaatt ccctatcagg 12180 gatcagggaa aggtgtcagc ttccagctcg tcaagctagg tgtctggaaa tccccaaccg 12240 acatgcaatc ctgggtcccc ttatcaacgg atgatccagt gatagacagg ctttacctct 12300 catctcacag aggtgttatc gctgacaatc aagcaaaatg ggctgtcccg acaacacgaa 12360 cagatgacaa gttgcgaatg gagacatgct tccaacaggc gtgtaagggt aaaatccaag 12420 cactctgcga gaatcccgag tgggcaccat tgaaggataa caggattcct tcatacgggg 12480 tcttgtctgt tgatctgagt ctgacagttg agcttaaaat caaaattgct tcgggattcg 12540 ggccattgat cacacacggt tcagggatgg acctatacaa atccaaccac aacaatgtgt 12600 attggctgac tatcccgcca atgaagaacc tagccttagg tgtaatcaac acattggagt 12660 ggataccgag attcaaggtt agtccctacc tcttcactgt cccaattaag gaagcaggcg 12720 aagactgcca tgccccaaca tacctacctg cggaggtgga tggtgatgtc aaactcagtt 12780 ccaatctggt gattctacct ggtcaagatc tccaatatgt tttggcaacc tacgatactt 12840 ccagggttga acatgctgtg gtttattacg tttacagccc aagccgctca ttttcttact 12900 tttatccttt taggttgcct ataaaggggg tccccatcga attacaagtg gaatgcttca 12960 catgggacca aaaactctgg tgccgtcact tctgtgtgct tgcggactca gaatctggtg 13020 gacatatcac tcactctggg atggtgggca tgggagtcag ctgcacagtc acccgggaag 13080 atggaaccaa tcgcagatag ggctgctagt gaaccaatca catgatgtca cccagacatc 13140 aggcataccc actagtgtga aatagacatc agaattaaga aaaacgtagg gtccaagtgg 13200 ttccccgtta tggactcgct atctgtcaac cagatcttat accctgaagt tcacctagat 13260 agcccgatag ttaccaataa gatagtagcc atcctggagt atgctcgagt ccctcacgct 13320 tacagcctgg aggaccctac actgtgtcag aacatcaagc accgcctaaa aaacggattt 13380 tccaaccaaa tgattataaa caatgtggaa gttgggaatg tcatcaagtc caagcttagg 13440 agttatccgg cccactctca tattccatat ccaaattgta atcaggattt atttaacata 13500 gaagacaaag agtcaacgag gaagatccgt gaactcctca aaaaggggaa ttcgctgtac 13560 tccaaagtca gtgataaggt tttccaatgc ttaagggaca ctaactcacg gcttggccta 13620 ggctccgaat tgagggagga catcaaggag aaagttatta acttgggagt ttacatgcac 13680 agctcccagt ggtttgagcc ctttctgttt tggtttacag tcaagactga gatgaggtca 13740 gtgattaaat cacaaaccca tacttgccat aggaggagac acacacctgt attcttcact 13800 ggtagttcag ttgagttgct aatctctcgt gaccttgttg ctataatcag taaagagtct 13860 caacatgtat attacctgac atttgaactg gttttgatgt attgtgatgt catagagggg 13920 aggttaatga cagagaccgc tatgactatt gatgctaggt atacagagct tctaggaaga 13980 gtcagataca tgtggaaact gatagatggt ttcttccctg cactcgggaa tccaacttat 14040 caaattgtag ccatgctgga gcctctttca cttgcttacc tgcagctgag ggatataaca 14100 gtagaactca gaggtgcttt ccttaaccac tgctttactg aaatacatga tgttcttgac 14160 caaaacgggt tttctgatga aggtacttat catgagttaa ctgaagctct agattacatt 14220 ttcataactg atgacataca tctgacaggg gagattttct catttttcag aagtttcggc 14280 caccccagac ttgaagcagt aacggctgct gaaaatgtta ggaaatacat gaatcagcct 14340 aaagtcattg tgtatgagac tctgatgaaa ggtcatgcca tattttgtgg aatcataatc 14400 aacggctatc gtgacaggca cggaggcagt tggccaccgc tgaccctccc cctgcatgct 14460 gcagacacaa tccggaatgc tcaagcttca ggtgaagggt taacacatga gcagtgcgtt 14520 gataactgga aatcttttgc tggagtgaaa tttggctgct ttatgcctct tagcctggat 14580 agtgatctga caatgtacct aaaggacaag gcacttgctg ctctccaaag ggaatgggat 14640 agtgatctga caatgtacct aaaggacaag gcacttgctg ctctccaaag ggaatgggat 14640 tcagtttacc cgaaagagtt cctgcgttac gaccctccca agggaaccgg gtcacggagg 14700 tcagtttacc cgaaagagtt cctgcgttac gaccctccca agggaaccgg gtcacggagg 14700 cttgtagatg ttttccttaa tgattcgagc tttgacccat atgatgtgat aatgtatgtt 14760 cttgtagatg ttttccttaa tgattcgagc tttgacccat atgatgtgat aatgtatgtt 14760 gtaagtggag cttacctcca tgaccctgag ttcaacctgt cttacagcct gaaagaaaag 14820 gtaagtggag cttacctcca tgaccctgag ttcaacctgt cttacagcct gaaagaaaag 14820 gagatcaagg aaacaggtag actttttgct aaaatgactt acaaaatgag ggcatgccaa 14880 gagatcaagg aaacaggtag actttttgct aaaatgactt acaaaatgag ggcatgccaa 14880 gtgattgctg aaaatctaat ctcaaacggg attggcaaat attttaagga caatgggatg 14940 gtgattgctg aaaatctaat ctcaaacggg attggcaaat attttaagga caatgggatg 14940 gccaaggatg agcacgattt gactaaggca ctccacactc tagctgtctc aggagtcccc 15000 gccaaggatg agcacgattt gactaaggca ctccacactc tagctgtctc aggagtcccc 15000 aaagatctca aagaaagtca cagggggggg ccagtcttaa aaacctactc ccgaagccca 15060 aaagatctca aagaaagtca cagggggggg ccagtcttaa aaacctactc ccgaagccca 15060 gtccacacaa gtaccaggaa cgtgagagca gcaaaagggt ttatagggtt ccctcaagta 15120 gtccacacaa gtaccaggaa cgtgagagca gcaaaagggt ttatagggtt ccctcaagta 15120 attcggcagg accaagacac tgatcatccg gagaatatgg aagcttacga gacagtcagt 15180 attcggcagg accaagacac tgatcatccg gagaatatgg aagcttacga gacagtcagt 15180 gcatttatca cgactgatct caagaagtac tgccttaatt ggagatatga gaccatcagc 15240 gcatttatca cgactgatct caagaagtac tgccttaatt ggagatatga gaccatcagc 15240 ttgtttgcac agaggctaaa tgagatttac ggattgccct catttttcca gtggctgcat 15300 aagaggcttg agacctctgt cctgtatgta agtgaccctc attgcccccc cgaccttgac 15360 gcccatatcc cgttatataa agtccccaat gatcaaatct tcattaagta ccctatggga 15420 ggtatagaag ggtattgtca gaagctgtgg accatcagca ccattcccta tctatacctg 15480 gctgcttatg agagcggagt aaggattgct tcgttagtgc aaggggacaa tcagaccata 15540 gccgtaacaa aaagggtacc cagcacatgg ccctacaacc ttaagaaacg ggaagctgct 15600 agagtaacta gagattactt tgtaattctt aggcaaaggc tacatgatat tggccatcac 15660 ctcaaggcaa atgagacaat tgtttcatca catttttttg tctattcaaa aggaatatat 15720 tatgatgggc tacttgtgtc ccaatcactc aagagcatcg caagatgtgt attctggtca 15780 gagactatag ttgatgaaac aagggcagca tgcagtaata ttgctacaac aatggctaaa 15840 agcatcgaga gaggttatga ccgttacctt gcatattccc tgaacgtcct aaaagtgata 15900 cagcaaattc tgatctctct tggcttcaca atcaattcaa ccatgacccg ggatgtagtc 15960 atacccctcc tcacaaacaa cgacctctta ataaggatgg cactgttgcc cgctcctatt 16020 ggggggatga attatctgaa tatgagcagg ctgtttgtca gaaacatcgg tgatccagta 16080 acatcatcaa ttgctgatct caagagaatg attctcgcct cactaatgcc tgaagagacc 16140 ctccatcaag taatgacaca acaaccgggg gactcttcat tcctagactg ggctagcgac 16200 ccttactcag caaatcttgt atgtgtccag agcatcacta gactcctcaa gaacataact 16260 gcaaggtttg tcctgatcca tagtccaaac ccaatgttaa aaggattatt ccatgatgac 16320 agtaaagaag aggacgaggg actggcggca ttcctcatgg acaggcatat tatagtacct 16380 agggcagctc atgaaatcct ggatcatagt gtcacagggg caagagagtc tattgcaggc 16440 atgctggata ccacaaaagg cttgattcga gccagcatga ggaagggggg gttaacctct 16500 cgagtgataa ccagattgtc caattatgac tatgaacaat tcagagcagg gatggtgcta 16560 ttgacaggaa gaaagagaaa tgtcctcatt gacaaagagt catgttcagt gcagctggcg 16620 agagctctaa gaagccatat gtgggcgagg ctagctcgag gacggcctat ttacggcctt 16680 gaggtccctg atgtactaga atctatgcga ggccacctta ttcggcgtca tgagacatgt 16740 gtcatctgcg agtgtggatc agtcaactac ggatggtttt ttgtcccctc gggttgccaa 16800 ctggatgata ttgacaagga aacatcatcc ttgagagtcc catatattgg ttctaccact 16860 gatgagagaa cagacatgaa gcttgccttc gtaagagccc caagtcgatc cttgcgatct 16920 gctgttagaa tagcaacagt gtactcatgg gcttacggtg atgatgatag ctcttggaac 16980 gaagcctggt tgttggctag gcaaagggcc aatgtgagcc tggaggagct aagggtgatc 17040 actcccatct caacttcgac taatttagcg cataggttga gggatcgtag cactcaagtg 17100 aaatactcag gtacatccct tgtccgagtg gcgaggtata ccacaatctc caacgacaat 17160 ctctcatttg tcatatcaga taagaaggtt gatactaact ttatatacca acaaggaatg 17220 cttctagggt tgggtgtttt agaaacattg tttcgactcg agaaagatac cggatcatct 17280 aacacggtat tacatcttca cgtcgaaaca gattgttgcg tgatcccgat gatagatcat 17340 cccaggatac ccagctcccg caagctagag ctgagggcag agctatgtac caacccattg 17400 atatatgata atgcaccttt aattgacaga gatgcaacaa ggctatacac ccagagccat 17460 aggaggcacc ttgtggaatt tgttacatgg tccacacccc aactatatca cattttagct 17520 aagtccacag cactatctat gattgacctg gtaacaaaat ttgagaagga ccatatgaat 17580 gaaatttcag ctctcatagg ggatgacgat atcaatagtt tcataactga gtttctgctc 17640 atagagccaa gattattcac tatctacttg ggccagtgtg cggccatcaa ttgggcattt 17700 gatgtacatt atcatagacc atcagggaaa tatcagatgg gtgagctgtt gtcatcgttc 17760 ctttctagaa tgagcaaagg agtgtttaag gtgcttgtca atgctctaag ccacccaaag 17820 atctacaaga aattctggca ttgtggtatt atagagccta tccatggtcc ttcacttgat 17880 gctcaaaact tgcacacaac tgtgtgcaac atggtttaca catgctatat gacctacctc 17940 gacctgttgt tgaatgaaga gttagaagag ttcacatttc tcttgtgtga aagcgacgag 18000 gatgtagtac cggacagatt cgacaacatc caggcaaaac acttatgtgt tctggcagat 18060 ttgtactgtc aaccagggac ctgcccacca attcgaggtc taagaccggt agagaaatgt 18120 gcagttctaa ccgaccatat caaggcagag gctatgttat ctccagcagg atcttcgtgg 18180 aacataaatc caattattgt agaccattac tcatgctctc tgacttatct ccggcgagga 18240 tcgatcaaac agataagatt gagagttgat ccaggattca ttttcgacgc cctcgctgag 18300 gtaaatgtca gtcagccaaa gatcggcagc aacaacatct caaatatgag catcaaggct 18360 ttcagacccc cacacgatga tgttgcaaaa ttgctcaaag atatcaacac aagcaagcac 18420 aatcttccca tttcaggggg caatctcgcc aattatgaaa tccatgcttt ccgcagaatc 18480 gggttgaact catctgcttg ctacaaagct gttgagatat caacattaat taggagatgc 18540 cttgagccag gggaggacgg cttgttcttg ggtgagggat cgggttctat gttgatcact 18600 tataaagaga tacttaaact aaacaagtgc ttctataata gtggggtttc cgccaattct 18660 agatctggtc aaagggaatt agcaccctat ccctccgaag ttggccttgt cgaacacaga 18720 atgggagtag gtaatattgt caaagtgctc tttaacggga ggcccgaagt cacgtgggta 18780 Methionine - glycine - serine - valine - asparagine - isoleucine - valine - lysine - valine - leucine - leucine - asparagine - glycine - arginine - serine - serine - arg - tryptophan - valine 18780 ggcagtgtag attgcttcaa tttcatagtt agtaatatcc ctacctctag tgtggggttt 18840 Glycine - serine - valine - isoleucine - alanine - serine - phenylalanine - histidine - valine - valine - isoleucine - proline - tyrosine - proline - serine - valine - glycine - phenylalanine 18840 atccattcag atatagagac cttgcctgac aaagatacta tagagaagct agaggaattg 18900 Isoleucine - proline - serine - isoleucine - arginine - threonine - alanine - aspartic - lysine - isoleucine - tyrosine - arginine - lysine - leucine - arginine - glutamic - leucine 18900 gcagccatct tatcgatggc tctgctcctg ggcaaaatag gatcaatact ggtgattaag 18960 Alanine - alanine - histidine - tyrosine - arginine - glycine - leucine - alanine - proline - glycine - lysine - asparagine - glycine - serine - asparagine - threonine - glycine - isoleucine - lysine 18960 cttatgcctt tcagcgggga ttttgttcag ggatttataa gttatgtagg gtctcattat 19020 Leucine - tyrosine - alanine - phenylalanine - serine - glycine - phenylalanine - valine - serine - glycine - phenylalanine - tyrosine - lysine - valine - methionine - arginine - serine - histidine - tyrosine 19020 agagaagtga accttgtata ccctagatac agcaacttca tctctactga atcttatttg 19080 Arginine - lysine - valine - asparagine - leucine - tyrosine - proline - arginine - threonine - serine - asparagine - serine - serine - threonine - glutamic - asparagine - leucine - phenylalanine 19080 gttatgacag atctcaaggc taaccggcta atgaatcctg aaaagattaa gcagcagata 19140 Valine - methionine - arginine - serine - lysine - alanine - asparagine - arginine - alanine - asparagine - glutamic - proline - lysine - isoleucine - lysine - alanine - alanine - aspartic 19140 attgaatcat ctgtgaggac ttcacctgga cttataggtc acatcctatc cattaagcaa 19200 Isoleucine - glutamic - histidine - leucine - valine - arginine - aspartic - phenylalanine - threonine - glycine - leucine - tyrosine - glycine - histidine - proline - tyrosine - proline - leucine - lysine - glutamine 19200 ctaagctgca tacaagcaat tgtgggagac gcagttagta gaggtgatat caatcctact 19260 Leucine - lysine - alanine - histidine - lysine - alanine - asparagine - cysteine - glycine - arginine - alanine - valine - serine - arginine - valine - isoleucine - glutamine - proline - threonine 19260 ctgaaaaaac ttacacctat agagcaggtg ctgatcaatt gcgggttggc aattaacgga 19320 Leucine - lysine - lysine - asparagine - leucine - threonine - tyrosine - arginine - serine - glycine - leucine - aspartic - glutamine - cysteine - glycine - valine - glycine - isoleucine - asparagine - glycine 19320 cctaagctgt gcaaagaatt gatccaccat gatgttgcct cagggcaaga tggattgctt 19380 Proline - lysine - alanine - valine - alanine - lysine - asparagine - aspartic - proline - histidine - methionine - valine - alanine - serine - glycine - lysine - methionine - aspartic - alanine - leucine 19380 aattctatac tcatcctcta cagggagttg gcaagattca aagacaacca aagaagtcaa 19440 caagggatgt tccacgctta ccccgtattg gtaagtagca ggcaacgaga acttatatct 19500 aggatcaccc gcaaattctg ggggcacatt cttctttact ccgggaacaa aaagttgata 19560 aataagttta tccagaatct caagtccggc tatctgatac tagacttaca ccagaatatc 19620 ttcgttaaga atctatccaa gtcagagaaa cagattatta tgacgggggg tttgaaacgt 19680 gagtgggttt ttaaggtaac agtcaaggag accaaagaat ggtataagtt agtcggatac 19740 agtgccctga ttaaggacta attggttgaa ctccggaacc ctaatcctgc cctaggtggt 19800 taggcattat ttgcaatata ttaaagaaaa ctttgaaaat acgaagtttc tattcccagc 19860 tttgtctggt ggccggcatg gtcccagcct cctcgctggc gccggctggg caacattccg 19920 aggggaccgt cccctcggta atggcgaatg ggacgcggcc gatccggctg ctaacaaagc 19980 ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa taactagcat aaccccttgg 20040 ggcctctaaa cgggtcttga ggggtttttt gctgaaagga ggaactatat ccggatgcgg 20100 ccgcgggccc tatggtaccc agcttttgtt ccctttagtg agggttaatt ccgagcttgg 20160 cgtaatcatg gtcatagctg tttcctgtgt gaaattgtta tccgctcaca attccacaca 20220 acataggagc cggaagcata aagtgtaaag cctggggtgc ctaatgagtg aggtaactca 20280 cattaattgc gttgcgctca ctgcccgctt tccagtcggg aaacctgtcg tgccagctgc 20340 attaatgaat cggccaacgc gcggggagag gcggtttgcg tattgggcgc tcttccgctt 20400 cctcgctcac tgactcgctg cgctcggtcg ttcggctgcg gcgagcggta tcagctcact 20460 caaaggcggt aatacggtta tccacagaat caggggataa cgcaggaaag aacatgtgag 20520 caaaaggcca gcaaaaggcc aggaaccgta aaaaggccgc gttgctggcg tttttccata 20580 ggctcggccc ccctgacgag catcacaaaa atcgacgctc aagtcagagg tggcgaaacc 20640 cgacaggact ataaagatac caggcgttcc cccctggaag ctccctcgtg cgctctcctg 20700 ttccgaccct gccgcttacc ggatacctgt ccgcctttct cccttcggga agcgtggcgc 20760 tttctcaatg ctcacgctgt aggtatctca gttcggtgta ggtcgttcgc tccaagctgg 20820 gctgtgtgca cgaacccccc gttcagcccg accgctgcgc cttatccggt aactatcgtc 20880 ttgagtccaa cccggtaaga cacgacttat cgccactggc agcagccact ggtaacagga 20940 ttagcagagc gaggtatgta ggcggtgcta cagagttctt gaagtggtgg cctaactacg 21000 gctacactag aaggacagta tttggtatct gcgctctgct gaagccagtt accttcggaa 21060 aaagagttgg tagctcttga tccggcaaac aaaccaccgc tggtagcggt ggtttttttg 21120 tttgcaagca gcagattacg cgcagaaaaa aaggatctca agaagatcct ttgatctttt 21180 ctacggggtc tgacgctcag tggaacgaaa actcacgtta agggattttg gtcatgagat 21240 tatcaaaaag gatcttcacc tagatccttt taaattaaaa atgaagtttt aaatcaatct 21300 aaagtatata tgagtaaact tggtctgaca gttaccaatg cttaatcagt gaggcaccta 21360 tctcagcgat ctgtctattt cgttcatcca tagttgcctg actgcccgtc gtgtagataa 21420 ctacgatacg ggagggctta ccatctggcc ccagtgctgc aatgataccg cgagacccac 21480 gctcaccggc tccagattta tcagcaataa accagccagc cggaagggcc gagcgcagaa 21540 gtggtcctgc aactttatcc gcctccatcc agtctattaa ttgttgccgg gaagctagag 21600 taagtagttc gccagttaat agtttgcgca acgttgttgc cattgctaca ggcatcgtgg 21660 tgtcacgctc gtcgtttggt atggcttcat tcagctccgg ttcccaacga tcaaggcgag 21720 ttacatgatc ccccatgttg tgaaaaaaag cggttagctc cttcggtcct ccgatcgttg 21780 tcagaagtaa gttggccgca gtgttatcac tcatgcttat ggcagcactg cataattctc 21840 ttactgtcat gccatccgta agatgctttt ctgtgactgg tgagtactca accaagtcat 21900 tctgagaata gtgtatgcgg cgaccgagtt gctcttgccc ggcgtcaata cgggataata 21960 ccgcgccaca tagcagaact ttaaaagtgc tcatcattgg aaaacgttct tcggggcgaa 22020 aactctcaag gatcttaccg ctgttgagat ccagttcgat gtaacccact cgtgcaccca 22080 actgatcttc agcatctttt actttcacca gcgtttctgg gtgagcaaaa acaggaaggc 22140 aaaatgccgc aaaaaaggga ataagggcga cacggaaatg ttgaatactc atactcttcc 22200 tttttcaata ttattgaagc atttatcagg gttattgtct catgagcgga tacatatttg 22260 aatgtattta gaaaaataaa caaatagggg ttccgcgcac atttccccga aaagtgccac 22320 ctgaaattgt aaacgttaat attttgttaa aattcgcgtt aaatttttgt taaatcagct 22380 cattttttaa ccaataggcc gaaatcggca aaatccctta taaatcaaaa gaatagaccg 22440 agatagggtt gagtgttgtt ccagtttgga acaagagtcc actattaaag aacgtggact 22500 ccaacgtcaa agggcgaaaa accgtctatc agggcgatgg cccactacgt gaaccatcac 22560 cctaatcaag ttttttgggg tcgaggtgcc gtaaagcact aaatcggaac cctaaaggga 22620 gcccccgatt tagagcttga cggggaaagc cggcgaacgt ggcgagaaag gaagggaaga 22680 aagcgaaagg agcgggcgct agggcgctgg caagtgtagc ggtcacgctg cgcgtaacca 22740 ccacacccgc cgcgcttaat gcgccgctac agggcgcgtc ccattcgcca ttcaggctgc 22800 gcaactgttg ggaagggcga tcggtgcggg cctcttcgct attacgccag ccaccgcggt 22860 g 22861 <210> 14 <211> 22861 <212> DNA <213> Artificial Sequence <220> <223> Plasmid MeV-Z+mNP+GPC <400> 14 gcggccgcta atacgactca ctatagggcc aactttgttt ggtctgatga gtccgtgagg 60 acgaaacccg gagtcccggg tcaccaaaca aagttgggta aggatagttc aatcaatgat 120 catcttctag tgcacttagg attcaagatc ctattatcag ggacaagagc aggattaggg 180 atatccgaga cgcgtacgat gggcaataag caggcaaagg cacccgaaag caaggattca 240 cctagagcat cactgattcc cgacgcaact catctggggc cacagttctg caaatcctgt 300 tggttcgaga acaaaggcct ggtggagtgc aataaccact acctgtgcct gaactgtctg 360 acactgctgc tgagtgtgag caacagatgc ccaatctgca agatgcctct gccaacaaag 420 ctgaggcctt ctgctgcacc caccgcacca ccaactggag ccgcagacag cattagaccc 480 cccccatact caccataagc gcgcagcgct tagacgtctc gcgatcgatt agtgcgagag 540 gccgagggcc agaacaacat ccgcctacca tccatcattg ttataaaaaa cttaggattc 600 aagatcctat tatcagggac aagagcagga ttagggatat ccgagatggc cacactttta 660 aggagcttag cattgttcaa aagaaacaag gacaaaccac ccattacatc aggatccggt 720 ggagccatca gaggaatcaa acacattatt atagtaccaa tccctggaga ttcctcaatt 780 accactcgat ccagacttct ggaccggttg gtgaggttaa ttggaaaccc ggatgtgagc 840 gggcccaaac taacaggggc actaataggt atattatcct tatttgtgga gtctccaggt 900 caattgattc agaggatcac cgatgaccct gacgttagca taaggctgtt agaggttgtc 960 cagagtgacc agtcacaatc tggccttacc ttcgcatcaa gaggtaccaa catggaggat 1020 gaggcggacc aatacttttc acatgatgat ccaattagta gtgatcaatc caggttcgga 1080 tggttcggga acaaggaaat ctcagatatt gaagtgcaag accctgaggg attcaacatg 1140 attctgggta ccatcctagc ccaaatttgg gtcttgctcg caaaggcggt tacggcccca 1200 gacacggcag ctgattcgga gctaagaagg tggataaagt acacccaaca aagaagggta 1260 gttggtgaat ttagattgga gagaaaatgg ttggatgtgg tgaggaacag gattgccgag 1320 gacctctcct tacgccgatt catggtcgct ctaatcctgg atatcaagag aacacccgga 1380 aacaaaccca ggattgctga aatgatatgt gacattgata catatatcgt agaggcagga 1440 ttagccagtt ttatcctgac tattaagttt gggatagaaa ctatgtatcc tgctcttgga 1500 ctgcatgaat ttgctggtga gttatccaca cttgagtcct tgatgaacct ttaccagcaa 1560 atgggggaaa ctgcacccta catggtaatc ctggagaact caattcagaa caagttcagt 1620 gcaggatcat accctctgct ctggagctat gccatgggag taggagtgga acttgaaaac 1680 tccatgggag gtttgaactt tggccgatct tactttgatc cagcatattt tagattaggg 1740 caagagatgg taaggaggtc agctggaaag gtcagttcca cattggcatc tgaactcggt 1800 atcactgccg aggatgcaag gcttgtttca gagattgcaa tgcatactac tgaggacaag 1860 atcagtagag cggttggacc cagacaagcc caagtatcat ttctacacgg tgatcaaagt 1920 gagaatgagc taccgagatt ggggggcaag gaagatagga gggtcaaaca gagtcgagga 1980 gaagccaggg agagctacag agaaaccggg cccagcagag caagtgatgc gagagctgcc 2040 catcttccaa ccggcacacc cctagacatt gacactgcaa cggagtccag ccaagatccg 2100 caggacagtc gaaggtcagc tgacgccctg cttaggctgc aagccatggc aggaatctcg 2160 gaagaacaag gctcagacac ggacacccct atagtgtaca atgacagaaa tcttctagac 2220 taggtgcgag aggccgaggg ccagaacaac atccgcctac catccatcat tgttataaaa 2280 aacttaggaa ccaggtccac acagccgcca gcccatcaac catccactcc cacgattgga 2340 gccaatggca gaagagcagg cacgccatgt caaaaacgga ctggaatgca tccgggctct 2400 caaggccgag cccatcggct cactggccat cgaggaagct atggcagcat ggtcagaaat 2460 atcagacaac ccaggacagg agcgagccac ctgcagggaa gagaaggcag gcagttcggg 2520 tctcagcaaa ccatgcctct cagcaattgg atcaactgaa ggcggtgcac ctcgcatccg 2580 cggtcaggga cctggagaga gcgatgacga cgctgaaact ttgggaatcc ccccaagaaa 2640 tctccaggca tcaagcactg ggttacagtg ttattacgtt tatgatcaca gcggtgaagc 2700 ggttaaggga atccaagatg ctgactctat catggttcaa tcaggccttg atggtgatag 2760 caccctctca ggaggagaca atgaatctga aaacagcgat gtggatattg gcgaacctga 2820 taccgaggga tatgctatca ctgaccgggg atctgctccc atctctatgg ggttcagggc 2880 ttctgatgtt gaaactgcag aaggagggga gatccacgag ctcctgagac tccaatccag 2940 aggcaacaac tttccgaagc ttgggaaaac tctcaatgtt cctccgcccc cggaccccgg 3000 tagggccagc acttccggga cacccattaa aaagggcaca gacgcgagat tagcctcatt 3060 tggaacggag atcgcgtctt tattgacagg tggtgcaacc caatgtgctc gaaagtcacc 3120 ctcggaacca tcagggccag gtgcacctgc ggggaatgtc cccgagtgtg tgagcaatgc 3180 cgcactgata caggagtgga cacccgaatc tggtaccaca atctccccga gatcccagaa 3240 taatgaagaa gggggagact attatgatga tgagctgttc tctgatgtcc aagatattaa 3300 aacagccttg gccaaaatac acgaggataa tcagaagata atctccaagc tagaatcact 3360 gctgttattg aagggagaag ttgagtcaat taagaagcag atcaacaggc aaaatatcag 3420 catatccacc ctggaaggac acctctcaag catcatgatc gccattcctg gacttgggaa 3480 ggatcccaac gaccccactg cagatgtcga aatcaatccc gacttgaaac ccatcatagg 3540 cagagattca ggccgagcac tggccgaagt tctcaagaaa cccgttgcca gccgacaact 3600 ccaaggaatg acaaatggac ggaccagttc cagaggacag ctgctgaagg aatttcagct 3660 aaagccgatc gggaaaaaga tgagctcagc cgtcgggttt gttcctgaca ccggccctgc 3720 atcacgcagt gtaatccgct ccattataaa atccagccgg ctagaggagg atcggaagcg 3780 ttacctgatg actctccttg atgatatcaa aggagccaat gatcttgcca agttccacca 3840 gatgctgatg aagataataa tgaagtagct acagctcaac ttacctgcca accccatgcc 3900 agtcgaccca actagcctac cctccatcat tgttataaaa aacttaggaa ccaggtccac 3960 acagccgcca gcccatcaac gcgtacgatg agtgccagca aagaaatcaa gagcttcctg 4020 tggacccaga gtctgcggag ggaactgagc ggatactgta gcaacatcaa actgcaggtg 4080 gtcaaggacg ctcaggcact gctgcatggg ctggacttct ccgaggtgtc taatgtgcag 4140 cggctgatgc ggaaagaacg gagggacgat aatgacctga agcgactgcg cgacctgaac 4200 caggcagtga acaatctggt cgagctgaag agcacccagc agaaatcaat cctgcgggtc 4260 gggacactga catctgacga cctgctgatc ctggctgcag acctggagaa gctgaaatcg 4320 aaagtgatcc gcaccgaaag gccactgtcc gccggggtct acatgggcaa tctgtcttcc 4380 cagcagctgg accagaggcg ggctctgctg aacatgattg ggatgtccgg aggaaatcag 4440 ggagctagag ccgggaggga cggagtcgtg cgggtctggg acgtgaagaa tgccgaactg 4500 ctgaacaacc agttcgggac catgccaagt ctgacactgg catgcctgac taaacagggc 4560 caggtggatc tgaatgatgc agtccaggct ctgaccgacc tgggcctgat ctacaccgcc 4620 aagtacccca atactagcga cctggataga ctgacccaga gccaccccat cctgaacatg 4680 atcgacacta agaagtcctc actgaacatc agtggctata atttctccct gggggcagca 4740 gtcaaggctg gcgcatgcat gctggacggc gggaatatgc tggaaaccat caaagtgtct 4800 ccccagacca tggatggcat cctgaaatct attctgaaag tcaagaaggc cctgggaatg 4860 tttatttcag acacccccgg cgagaggaat ccatatgaga acattctgta taagatttgc 4920 ctgagtggcg acgggtggcc atacattgca agccggacat caattaccgg aagagcttgg 4980 gagaatacag tcgtggacct ggaaagcgac ggcaagcccc agaaggccga ctcaaacaac 5040 tcctcaaaga gtctgcagtc agctggcttc acagcagggc tgacttactc ccagctgatg 5100 acactgaagg acgcaatgct gcagctggac ccaaacgcta agacatggat ggccatcgag 5160 gcccggccag aagatccagt ggaaatcgca ctgtatcagc catcatccgg atgctatatc 5220 catttcttcc gggaaccaac tgatctgaag cagttcaagc aggatgcaaa gtactcccac 5280 ggaatcgatg tcaccgatct gttcgcaacc cagccaggac tgacatcagc cgtcatcgat 5340 gccctgccta ggaacatggt cattacttgc cagggctccg acgatattag gaagctgctg 5400 gagagccagg gacggaagga tatcaaactg atcgatattg ccctgtctaa gactgatagc 5460 cggaaatatg agaatgcagt ctgggatcag tacaaggacc tgtgccatat gcataccgga 5520 gtggtcgtcg agaagaagaa gaggggcgga aaggaagaga tcacacccca ctgtgccctg 5580 atggattgca tcatgttcga cgcagccgtg tccgggggcc tgaacacctc agtcctgagg 5640 gctgtcctgc caagagatat ggtgtttaga acttcaaccc caagagtcgt cctgtaattc 5700 gaactacagc tcaacttacc tgccaacccc atgccagtcg acccaactag tacaacctaa 5760 atccattata aaaaacttag gaaccaggtc cacacagccg ccagcccatc aaccatccac 5820 tcccacgatt ggaggccggc catgggccag attgtcacat tctttcagga agtgccacac 5880 gtcattgagg aggtcatgaa catcgtgctg attgctctgt cagtgctggc agtgctgaaa 5940 ggactgtaca acttcgctac ctgtggactg gtgggactgg tcacattcct gctgctgtgc 6000 ggcagaagtt gcactacctc actgtacaaa ggagtgtacg agctgcagac tctggaactg 6060 aacatggaga cactgaatat gacaatgcct ctgagctgca ccaagaataa tagccaccac 6120 tatatcatgg tcgggaacga aaccggcctg gaactgaccc tgacaaacac cagcatcatt 6180 aaccacaagt tctgcaatct gagcgacgct cacaagaaga acctgtatga ccacgctctg 6240 atgtccatca tcagtacctt tcacctgtcc atccccaatt tcaaccagta cgaggcaatg 6300 tcatgcgact tcaacggggg caagatcagt gtccagtaca acctgagcca ctcctacgcc 6360 ggcgacgcag ccaaccactg cggaactgtc gccaatggcg tgctgcagac attcatgagg 6420 atggcatggg ggggatctta catcgcactg gatagcggca ggggcaattg ggattgcatc 6480 atgacttcct atcagtatct gattatccag aatactacat gggaggatca ttgccagttc 6540 agtcggccca gccctattgg atatctgggg ctgctgtcac agagaacacg ggatatctat 6600 atttcaagac gcctgctggg cacattcact tggacactgt cagacagtga gggcaaggat 6660 actccagggg gctactgcct gacacgatgg atgctgatcg aagcagagct gaaatgcttc 6720 ggcaataccg cagtggccaa gtgcaacgag aaacacgacg aggagttctg cgacatgctg 6780 aggctgttcg acttcaacaa acaggctatc cagagactga aggcagaagc ccagatgtca 6840 atccagctga tcaacaaggc agtgaacgcc ctgatcaacg accagctgat catgaagaac 6900 cacctgagag acattatggg catcccctac tgtaattaca gcaagtattg gtacctgaac 6960 cacactacaa ccgggagaac atccctgccc aagtgctggc tggtcagcaa tgggagttat 7020 ctgaatgaaa cccatttcag cgacgatatc gaacagcagg ctgacaacat gatcacagag 7080 atgctgcaga aagagtacat ggaaagacag ggcaagacac cactgggact ggtcgatctg 7140 ttcgtcttct ccactagctt ctatctgatt tccatcttcc tgcacctggt gaagatcccc 7200 actcataggc acattgtcgg caagagttgc cctaaacccc ataggctgaa tcacatgggg 7260 atttgtagtt gcggcctgta taagcagcct ggcgtgcctg tgaagtggaa gagatgagcg 7320 cgcagcgctt agacgtctcg cgatcgatac tagtacaacc taaatccatt ataaaaaact 7380 taggagcaaa gtgattgcct cccaaggtcc acaatgacag agacctacga cttcgacaag 7440 tcggcatggg acatcaaagg gtcgatcgct ccgatacaac ccaccaccta cagtgatggc 7500 aggctggtgc cccaggtcag agtcatagat cctggtctag gcgacaggaa ggatgaatgc 7560 tttatgtaca tgtttctgct gggggttgtt gaggacagcg attccctagg gcctccaatc 7620 gggcgagcat ttgggttcct gcccttaggt gttggcagat ccacagcaaa gcccgaaaaa 7680 ctcctcaaag aggccactga gcttgacata gttgttagac gtacagcagg gctcaatgaa 7740 aaactggtgt tctacaacaa caccccacta actctcctca caccttggag aaaggtccta 7800 acaacaggga gtgtcttcaa cgcaaaccaa gtgtgcaatg cggttaatct gataccgctc 7860 gataccccgc agaggttccg tgttgtttat atgagcatca cccgtctttc ggataacggg 7920 tattacaccg ttcctagaag aatgctggaa ttcagatcgg tcaatgcagt ggccttcaac 7980 ctgctggtga cccttaggat tgacaaggcg ataggccctg ggaagatcat cgacaataca 8040 gagcaacttc ctgaggcaac atttatggtc cacatcggga acttcaggag aaagaagagt 8100 gaagtctact ctgccgatta ttgcaaaatg aaaatcgaaa agatgggcct ggtttttgca 8160 cttggtggga tagggggcac cagtcttcac attagaagca caggcaaaat gagcaagact 8220 ctccatgcac aactcgggtt caagaagacc ttatgttacc cgctgatgga tatcaatgaa 8280 gaccttaatc gattactctg gaggagcaga tgcaagatag taagaatcca ggcagttttg 8340 cagccatcag ttcctcaaga attccgcatt tacgacgacg tgatcataaa tgatgaccaa 8400 ggactattca aagttctgta gaccgtagtg cccagcaatg cccgaaaacg acccccctca 8460 caatgacagc cagaaggccc ggacaaaaaa gccccctccg aaagactcca cggaccaagc 8520 gagaggccag ccagcagccg acggcaagcg cgaacaccag gcggccccag cacagaacag 8580 ccctgacaca aggccaccac cagccacccc aatctgcatc ctcctcgtgg gacccccgag 8640 gaccaacccc caaggctgcc cccgatccaa accaccaacc gcatccccac cacccccggg 8700 aaagaaaccc ccagcaattg gaaggcccct ccccctcttc ctcaacacaa gaactccaca 8760 accgaaccgc acaagcgacc gaggtgaccc aaccgcaggc atccgactcc ctagacagat 8820 cctctctccc cggcaaacta aacaaaactt agggccaagg aacatacaca cccaacagaa 8880 cccagacccc ggcccacggc gccgcgcccc caacccccga caaccagagg gagcccccaa 8940 ccaatcccgc cggctccccc ggtgcccaca ggcagggaca ccaacccccg aacagaccca 9000 gcacccaacc atcgacaatc caagacgggg gggccccccc aaaaaaaggc ccccaggggc 9060 cgacagccag caccgcgagg aagcccaccc accccacaca cgaccacggc aaccaaacca 9120 gaacccagac caccctgggc caccagctcc cagactcggc catcaccccg cagaaaggaa 9180 aggccacaac ccgcgcaccc cagccccgat ccggcgggga gccacccaac ccgaaccagc 9240 acccaagagc gatccccgaa ggacccccga accgcaaagg acatcagtat cccacagcct 9300 ctccaagtcc cccggtctcc tcctcttctc gaagggacca aaagatcaat ccaccacacc 9360 cgacgacact caactcccca cccctaaagg agacaccggg aatcccagaa tcaagactca 9420 tccaatgtcc atcatgggtc tcaaggtgaa cgtctctgcc atattcatgg cagtactgtt 9480 aactctccaa acacccaccg gtcaaatcca ttggggcaat ctctctaaga taggggtggt 9540 aggaatagga agtgcaagct acaaagttat gactcgttcc agccatcaat cattagtcat 9600 aaaattaatg cccaatataa ctctcctcaa taactgcacg agggtagaga ttgcagaata 9660 caggagacta ctgagaacag ttttggaacc aattagagat gcacttaatg caatgaccca 9720 gaatataaga ccggttcaga gtgtagcttc aagtaggaga cacaagagat ttgcgggagt 9780 agtcctggca ggtgcggccc taggcgttgc cacagctgct cagataacag ccggcattgc 9840 acttcaccag tccatgctga actctcaagc catcgacaat ctgagagcga gcctggaaac 9900 tactaatcag gcaattgaga caatcagaca agcagggcag gagatgatat tggctgttca 9960 gggtgtccaa gactacatca ataatgagct gataccgtct atgaaccaac tatcttgtga 10020 tttaatcggc cagaagctcg ggctcaaatt gctcagatac tatacagaaa tcctgtcatt 10080 atttggcccc agtttacggg accccatatc tgcggagata tctatccagg ctttgagcta 10140 tgcgcttgga ggagacatca ataaggtgtt agaaaagctc ggatacagtg gaggtgattt 10200 actgggcatc ttagagagcg gaggaataaa ggcccggata actcacgtcg acacagagtc 10260 ctacttcatt gtcctcagta tagcctatcc gacgctgtcc gagattaagg gggtgattgt 10320 ccaccggcta gagggggtct cgtacaacat aggctctcaa gagtggtata ccactgtgcc 10380 caagtatgtt gcaacccaag ggtaccttat ctcgaatttt gatgagtcat cgtgtacttt 10440 catgccagag gggactgtgt gcagccaaaa tgccttgtac ccgatgagtc ctctgctcca 10500 agaatgcctc cgggggtaca ccaagtcctg tgctcgtaca ctcgtatccg ggtcttttgg 10560 gaaccggttc attttatcac aagggaacct aatagccaat tgtgcatcaa tcctttgcaa 10620 gtgttacaca acaggaacga tcattaatca agaccctgac aagatcctaa catacattgc 10680 gtgttacaca acaggaacga tcattaatca agaccctgac aagatcctaa catacattgc 10680 tgccgatcac tgcccggtag tcgaggtgaa cggcgtgacc atccaagtcg ggagcaggag 10740 tgccgatcac tgcccggtag tcgaggtgaa cggcgtgacc atccaagtcg ggagcaggag 10740 gtatccagac gctgtgtact tgcacagaat tgacctcggt cctcccatat cattggagag 10800 gtatccagac gctgtgtact tgcacagaat tgacctcggt cctcccatat cattggagag 10800 gttggacgta gggacaaatc tggggaatgc aattgctaag ttggaggatg ccaaggaatt 10860 gttggacgta gggacaaatc tggggaatgc aattgctaag ttggaggatg ccaaggaatt 10860 gttggagtca tcggaccaga tattgaggag tatgaaaggt ttatcgagca ctagcatagt 10920 gttggagtca tcggaccaga tattgaggag tatgaaaggt ttatcgagca ctagcatagt 10920 ctacatcctg attgcagtgt gtcttggagg gttgataggg atccccgctt taatatgttg 10980 ctacatcctg attgcagtgt gtcttggagg gttgataggg atccccgctt taatatgttg 10980 ctgcaggggg cgttgtaaca aaaagggaga acaagttggt atgtcaagac caggcctaaa 11040 ctgcaggggg cgttgtaaca aaaagggaga acaagttggt atgtcaagac caggcctaaa 11040 gcctgatctt acgggaacat caaaatccta tgtaaggtcg ctctgatcct ctacaactct 11100 gcctgatctt acgggaacat caaaatccta tgtaaggtcg ctctgatcct ctacaactct 11100 tgaaacacaa atgtcccaca agtctcctct tcgtcatcaa gcaaccaccg cacccagcat 11160 tgaaacacaa atgtcccaca agtctcctct tcgtcatcaa gcaaccaccg cacccagcat 11160 caagcccacc tgaaattatc tccggcttcc ctctggccga acaatatcgg tagttaatca 11220 caagcccacc tgaaattatc tccggcttcc ctctggccga acaatatcgg tagttaatca 11220 aaacttaggg tgcaagatca tccacaatgt caccacaacg agaccggata aatgccttct 11280 aaacttaggg tgcaagatca tccacaatgt caccacaacg agaccggata aatgccttct 11280 acaaagataa cccccatccc aagggaagta ggatagtcat taacagagaa catcttatga 11340 ttgatagacc ttatgttttg ctggctgttc tgtttgtcat gtttctgagc ttgatcgggt 11400 tgctagccat tgcaggcatt agacttcatc gggcagccat ctacaccgca gagatccata 11460 aaagcctcag caccaatcta gatgtaacta actcaatcga gcatcaggtc aaggacgtgc 11520 tgacaccact cttcaaaatc atcggtgatg aagtgggcct gaggacacct cagagattca 11580 ctgacctagt gaaattaatc tctgacaaga ttaaattcct taatccggat agggagtacg 11640 acttcagaga tctcacttgg tgtatcaacc cgccagagag aatcaaattg gattatgatc 11700 aatactgtgc agatgtggct gctgaagagc tcatgaatgc attggtgaac tcaactctac 11760 tggagaccag aacaaccaat cagttcctag ctgtctcaaa gggaaactgc tcagggccca 11820 ctacaatcag aggtcaattc tcaaacatgt cgctgtccct gttagacttg tatttaggtc 11880 gaggttacaa tgtgtcatct atagtcacta tgacatccca gggaatgtat gggggaactt 11940 acctagtgga aaagcctaat ctgagcagca aaaggtcaga gttgtcacaa ctgagcatgt 12000 accgagtgtt tgaagtaggt gttatcagaa atccgggttt gggggctccg gtgttccata 12060 tgacaaacta tcttgagcaa ccagtcagta atgatctcag caactgtatg gtggctttgg 12120 gggagctcaa actcgcagcc ctttgtcacg gggaagattc tatcacaatt ccctatcagg 12180 gatcagggaa aggtgtcagc ttccagctcg tcaagctagg tgtctggaaa tccccaaccg 12240 acatgcaatc ctgggtcccc ttatcaacgg atgatccagt gatagacagg ctttacctct 12300 catctcacag aggtgttatc gctgacaatc aagcaaaatg ggctgtcccg acaacacgaa 12360 cagatgacaa gttgcgaatg gagacatgct tccaacaggc gtgtaagggt aaaatccaag 12420 cactctgcga gaatcccgag tgggcaccat tgaaggataa caggattcct tcatacgggg 12480 tcttgtctgt tgatctgagt ctgacagttg agcttaaaat caaaattgct tcgggattcg 12540 ggccattgat cacacacggt tcagggatgg acctatacaa atccaaccac aacaatgtgt 12600 attggctgac tatcccgcca atgaagaacc tagccttagg tgtaatcaac acattggagt 12660 ggataccgag attcaaggtt agtccctacc tcttcactgt cccaattaag gaagcaggcg 12720 aagactgcca tgccccaaca tacctacctg cggaggtgga tggtgatgtc aaactcagtt 12780 ccaatctggt gattctacct ggtcaagatc tccaatatgt tttggcaacc tacgatactt 12840 ccagggttga acatgctgtg gtttattacg tttacagccc aagccgctca ttttcttact 12900 tttatccttt taggttgcct ataaaggggg tccccatcga attacaagtg gaatgcttca 12960 catgggacca aaaactctgg tgccgtcact tctgtgtgct tgcggactca gaatctggtg 13020 gacatatcac tcactctggg atggtgggca tgggagtcag ctgcacagtc acccgggaag 13080 atggaaccaa tcgcagatag ggctgctagt gaaccaatca catgatgtca cccagacatc 13140 aggcataccc actagtgtga aatagacatc agaattaaga aaaacgtagg gtccaagtgg 13200 ttccccgtta tggactcgct atctgtcaac cagatcttat accctgaagt tcacctagat 13260 agcccgatag ttaccaataa gatagtagcc atcctggagt atgctcgagt ccctcacgct 13320 tacagcctgg aggaccctac actgtgtcag aacatcaagc accgcctaaa aaacggattt 13380 tccaaccaaa tgattataaa caatgtggaa gttgggaatg tcatcaagtc caagcttagg 13440 tccaaccaaa tgattataaa caatgtggaa gttgggaatg tcatcaagtc caagcttagg 13440 agttatccgg cccactctca tattccatat ccaaattgta atcaggattt atttaacata 13500 agttatccgg cccactctca tattccatat ccaaattgta atcaggattt atttaacata 13500 gaagacaaag agtcaacgag gaagatccgt gaactcctca aaaaggggaa ttcgctgtac 13560 gaagacaaag agtcaacgag gaagatccgt gaactcctca aaaaggggaa ttcgctgtac 13560 tccaaagtca gtgataaggt tttccaatgc ttaagggaca ctaactcacg gcttggccta 13620 tccaaagtca gtgataaggt tttccaatgc ttaagggaca ctaactcacg gcttggccta 13620 ggctccgaat tgagggagga catcaaggag aaagttatta acttgggagt ttacatgcac 13680 ggctccgaat tgagggagga catcaaggag aaagttatta acttgggagt ttacatgcac 13680 agctcccagt ggtttgagcc ctttctgttt tggtttacag tcaagactga gatgaggtca 13740 agctcccagt ggtttgagcc ctttctgttt tggtttacag tcaagactga gatgaggtca 13740 gtgattaaat cacaaaccca tacttgccat aggaggagac acacacctgt attcttcact 13800 gtgattaaat cacaaaccca tacttgccat aggaggagac acacacctgt attcttcact 13800 ggtagttcag ttgagttgct aatctctcgt gaccttgttg ctataatcag taaagagtct 13860 ggtagttcag ttgagttgct aatctctcgt gaccttgttg ctataatcag taaagagtct 13860 caacatgtat attacctgac atttgaactg gttttgatgt attgtgatgt catagagggg 13920 caacatgtat attacctgac atttgaactg gttttgatgt attgtgatgt catagagggg 13920 aggttaatga cagagaccgc tatgactatt gatgctaggt atacagagct tctaggaaga 13980 aggttaatga cagagaccgc tatgactatt gatgctaggt atacagagct tctaggaaga 13980 gtcagataca tgtggaaact gatagatggt ttcttccctg cactcgggaa tccaacttat 14040 gtcagataca tgtggaaact gatagatggt ttcttccctg cactcgggaa tccaacttat 14040 caaattgtag ccatgctgga gcctctttca cttgcttacc tgcagctgag ggatataaca 14100 gtagaactca gaggtgcttt ccttaaccac tgctttactg aaatacatga tgttcttgac 14160 caaaacgggt tttctgatga aggtacttat catgagttaa ctgaagctct agattacatt 14220 ttcataactg atgacataca tctgacaggg gagattttct catttttcag aagtttcggc 14280 caccccagac ttgaagcagt aacggctgct gaaaatgtta ggaaatacat gaatcagcct 14340 aaagtcattg tgtatgagac tctgatgaaa ggtcatgcca tattttgtgg aatcataatc 14400 aacggctatc gtgacaggca cggaggcagt tggccaccgc tgaccctccc cctgcatgct 14460 gcagacacaa tccggaatgc tcaagcttca ggtgaagggt taacacatga gcagtgcgtt 14520 gataactgga aatcttttgc tggagtgaaa tttggctgct ttatgcctct tagcctggat 14580 agtgatctga caatgtacct aaaggacaag gcacttgctg ctctccaaag ggaatgggat 14640 tcagtttacc cgaaagagtt cctgcgttac gaccctccca agggaaccgg gtcacggagg 14700 cttgtagatg ttttccttaa tgattcgagc tttgacccat atgatgtgat aatgtatgtt 14760 gtaagtggag cttacctcca tgaccctgag ttcaacctgt cttacagcct gaaagaaaag 14820 gtaagtggag cttacctcca tgaccctgag ttcaacctgt cttacagcct gaaagaaaag 14820 gagatcaagg aaacaggtag actttttgct aaaatgactt acaaaatgag ggcatgccaa 14880 gagatcaagg aaacaggtag actttttgct aaaatgactt acaaaatgag ggcatgccaa 14880 gtgattgctg aaaatctaat ctcaaacggg attggcaaat attttaagga caatgggatg 14940 gtgattgctg aaaatctaat ctcaaacggg attggcaaat attttaagga caatgggatg 14940 gccaaggatg agcacgattt gactaaggca ctccacactc tagctgtctc aggagtcccc 15000 gccaaggatg agcacgattt gactaaggca ctccacactc tagctgtctc aggagtcccc 15000 aaagatctca aagaaagtca cagggggggg ccagtcttaa aaacctactc ccgaagccca 15060 aaagatctca aagaaagtca cagggggggg ccagtcttaa aaacctactc ccgaagccca 15060 gtccacacaa gtaccaggaa cgtgagagca gcaaaagggt ttatagggtt ccctcaagta 15120 gtccacacaa gtaccaggaa cgtgagagca gcaaaagggt ttatagggtt ccctcaagta 15120 attcggcagg accaagacac tgatcatccg gagaatatgg aagcttacga gacagtcagt 15180 attcggcagg accaagacac tgatcatccg gagaatatgg aagcttacga gacagtcagt 15180 gcatttatca cgactgatct caagaagtac tgccttaatt ggagatatga gaccatcagc 15240 gcatttatca cgactgatct caagaagtac tgccttaatt ggagatatga gaccatcagc 15240 ttgtttgcac agaggctaaa tgagatttac ggattgccct catttttcca gtggctgcat 15300 ttgtttgcac agaggctaaa tgagatttac ggattgccct catttttcca gtggctgcat 15300 aagaggcttg agacctctgt cctgtatgta agtgaccctc attgcccccc cgaccttgac 15360 aagaggcttg agacctctgt cctgtatgta agtgaccctc attgcccccc cgaccttgac 15360 gcccatatcc cgttatataa agtccccaat gatcaaatct tcattaagta ccctatggga 15420 gcccatatcc cgttatataa agtccccaat gatcaaatct tcattaagta ccctatggga 15420 ggtatagaag ggtattgtca gaagctgtgg accatcagca ccattcccta tctatacctg 15480 gctgcttatg agagcggagt aaggattgct tcgttagtgc aaggggacaa tcagaccata 15540 gccgtaacaa aaagggtacc cagcacatgg ccctacaacc ttaagaaacg ggaagctgct 15600 agagtaacta gagattactt tgtaattctt aggcaaaggc tacatgatat tggccatcac 15660 ctcaaggcaa atgagacaat tgtttcatca catttttttg tctattcaaa aggaatatat 15720 tatgatgggc tacttgtgtc ccaatcactc aagagcatcg caagatgtgt attctggtca 15780 gagactatag ttgatgaaac aagggcagca tgcagtaata ttgctacaac aatggctaaa 15840 agcatcgaga gaggttatga ccgttacctt gcatattccc tgaacgtcct aaaagtgata 15900 cagcaaattc tgatctctct tggcttcaca atcaattcaa ccatgacccg ggatgtagtc 15960 atacccctcc tcacaaacaa cgacctctta ataaggatgg cactgttgcc cgctcctatt 16020 ggggggatga attatctgaa tatgagcagg ctgtttgtca gaaacatcgg tgatccagta 16080 acatcatcaa ttgctgatct caagagaatg attctcgcct cactaatgcc tgaagagacc 16140 ctccatcaag taatgacaca acaaccgggg gactcttcat tcctagactg ggctagcgac 16200 ccttactcag caaatcttgt atgtgtccag agcatcacta gactcctcaa gaacataact 16260 gcaaggtttg tcctgatcca tagtccaaac ccaatgttaa aaggattatt ccatgatgac 16320 agtaaagaag aggacgaggg actggcggca ttcctcatgg acaggcatat tatagtacct 16380 agggcagctc atgaaatcct ggatcatagt gtcacagggg caagagagtc tattgcaggc 16440 atgctggata ccacaaaagg cttgattcga gccagcatga ggaagggggg gttaacctct 16500 cgagtgataa ccagattgtc caattatgac tatgaacaat tcagagcagg gatggtgcta 16560 ttgacaggaa gaaagagaaa tgtcctcatt gacaaagagt catgttcagt gcagctggcg 16620 agagctctaa gaagccatat gtgggcgagg ctagctcgag gacggcctat ttacggcctt 16680 gaggtccctg atgtactaga atctatgcga ggccacctta ttcggcgtca tgagacatgt 16740 gtcatctgcg agtgtggatc agtcaactac ggatggtttt ttgtcccctc gggttgccaa 16800 ctggatgata ttgacaagga aacatcatcc ttgagagtcc catatattgg ttctaccact 16860 ctggatgata ttgacaagga aacatcatcc ttgagagtcc catatattgg ttctaccact 16860 gatgagagaa cagacatgaa gcttgccttc gtaagagccc caagtcgatc cttgcgatct 16920 gatgagagaa cagacatgaa gcttgccttc gtaagagccc caagtcgatc cttgcgatct 16920 gctgttagaa tagcaacagt gtactcatgg gcttacggtg atgatgatag ctcttggaac 16980 gctgttagaa tagcaacagt gtactcatgg gcttacggtg atgatgatag ctcttggaac 16980 gaagcctggt tgttggctag gcaaagggcc aatgtgagcc tggaggagct aagggtgatc 17040 gaagcctggt tgttggctag gcaaagggcc aatgtgagcc tggaggagct aagggtgatc 17040 actcccatct caacttcgac taatttagcg cataggttga gggatcgtag cactcaagtg 17100 actcccatct caacttcgac taatttagcg cataggttga gggatcgtag cactcaagtg 17100 aaatactcag gtacatccct tgtccgagtg gcgaggtata ccacaatctc caacgacaat 17160 aaatactcag gtacatccct tgtccgagtg gcgaggtata ccacaatctc caacgacaat 17160 ctctcatttg tcatatcaga taagaaggtt gatactaact ttatatacca acaaggaatg 17220 ctctcatttg tcatatcaga taagaaggtt gatactaact ttatatacca acaaggaatg 17220 cttctagggt tgggtgtttt agaaacattg tttcgactcg agaaagatac cggatcatct 17280 cttctagggt tgggtgtttt agaaacattg tttcgactcg agaaagatac cggatcatct 17280 aacacggtat tacatcttca cgtcgaaaca gattgttgcg tgatcccgat gatagatcat 17340 aacacggtat tacatcttca cgtcgaaaca gattgttgcg tgatcccgat gatagatcat 17340 cccaggatac ccagctcccg caagctagag ctgagggcag agctatgtac caacccattg 17400 cccaggatac ccagctcccg caagctagag ctgagggcag agctatgtac caacccattg 17400 atatatgata atgcaccttt aattgacaga gatgcaacaa ggctatacac ccagagccat 17460 atatatgata atgcaccttt aattgacaga gatgcaacaa ggctatacac ccagagccat 17460 aggaggcacc ttgtggaatt tgttacatgg tccacacccc aactatatca cattttagct 17520 aggaggcacc ttgtggaatt tgttacatgg tccacacccc aactatatca cattttagct 17520 aagtccacag cactatctat gattgacctg gtaacaaaat ttgagaagga ccatatgaat 17580 gaaatttcag ctctcatagg ggatgacgat atcaatagtt tcataactga gtttctgctc 17640 atagagccaa gattattcac tatctacttg ggccagtgtg cggccatcaa ttgggcattt 17700 gatgtacatt atcatagacc atcagggaaa tatcagatgg gtgagctgtt gtcatcgttc 17760 ctttctagaa tgagcaaagg agtgtttaag gtgcttgtca atgctctaag ccacccaaag 17820 atctacaaga aattctggca ttgtggtatt atagagccta tccatggtcc ttcacttgat 17880 gctcaaaact tgcacacaac tgtgtgcaac atggtttaca catgctatat gacctacctc 17940 gacctgttgt tgaatgaaga gttagaagag ttcacatttc tcttgtgtga aagcgacgag 18000 gatgtagtac cggacagatt cgacaacatc caggcaaaac acttatgtgt tctggcagat 18060 ttgtactgtc aaccagggac ctgcccacca attcgaggtc taagaccggt agagaaatgt 18120 gcagttctaa ccgaccatat caaggcagag gctatgttat ctccagcagg atcttcgtgg 18180 aacataaatc caattattgt agaccattac tcatgctctc tgacttatct ccggcgagga 18240 tcgatcaaac agataagatt gagagttgat ccaggattca ttttcgacgc cctcgctgag 18300 gtaaatgtca gtcagccaaa gatcggcagc aacaacatct caaatatgag catcaaggct 18360 ttcagacccc cacacgatga tgttgcaaaa ttgctcaaag atatcaacac aagcaagcac 18420 aatcttccca tttcaggggg caatctcgcc aattatgaaa tccatgcttt ccgcagaatc 18480 gggttgaact catctgcttg ctacaaagct gttgagatat caacattaat taggagatgc 18540 cttgagccag gggaggacgg cttgttcttg ggtgagggat cgggttctat gttgatcact 18600 tataaagaga tacttaaact aaacaagtgc ttctataata gtggggtttc cgccaattct 18660 agatctggtc aaagggaatt agcaccctat ccctccgaag ttggccttgt cgaacacaga 18720 atgggagtag gtaatattgt caaagtgctc tttaacggga ggcccgaagt cacgtgggta 18780 ggcagtgtag attgcttcaa tttcatagtt agtaatatcc ctacctctag tgtggggttt 18840 atccattcag atatagagac cttgcctgac aaagatacta tagagaagct agaggaattg 18900 gcagccatct tatcgatggc tctgctcctg ggcaaaatag gatcaatact ggtgattaag 18960 gcagccatct tatcgatggc tctgctcctg ggcaaaatag gatcaatact ggtgattaag 18960 cttatgcctt tcagcgggga ttttgttcag ggatttataa gttatgtagg gtctcattat 19020 cttatgcctt tcagcgggga ttttgttcag ggatttataa gttatgtagg gtctcattat 19020 agagaagtga accttgtata ccctagatac agcaacttca tctctactga atcttatttg 19080 agagaagtga accttgtata ccctagatac agcaacttca tctctactga atcttatttg 19080 gttatgacag atctcaaggc taaccggcta atgaatcctg aaaagattaa gcagcagata 19140 gttatgacag atctcaaggc taaccggcta atgaatcctg aaaagattaa gcagcagata 19140 attgaatcat ctgtgaggac ttcacctgga cttataggtc acatcctatc cattaagcaa 19200 attgaatcat ctgtgaggac ttcacctgga cttataggtc acatcctatc cattaagcaa 19200 ctaagctgca tacaagcaat tgtgggagac gcagttagta gaggtgatat caatcctact 19260 ctaagctgca tacaagcaat tgtgggagac gcagttagta gaggtgatat caatcctact 19260 ctgaaaaaac ttacacctat agagcaggtg ctgatcaatt gcgggttggc aattaacgga 19320 ctgaaaaaac ttacacctat agagcaggtg ctgatcaatt gcgggttggc aattaacgga 19320 cctaagctgt gcaaagaatt gatccaccat gatgttgcct cagggcaaga tggattgctt 19380 cctaagctgt gcaaagaatt gatccaccat gatgttgcct cagggcaaga tggattgctt 19380 aattctatac tcatcctcta cagggagttg gcaagattca aagacaacca aagaagtcaa 19440 aattctatac tcatcctcta cagggagttg gcaagattca aagacaacca aagaagtcaa 19440 caagggatgt tccacgctta ccccgtattg gtaagtagca ggcaacgaga acttatatct 19500 caagggatgt tccacgctta ccccgtattg gtaagtagca ggcaacgaga acttatatct 19500 aggatcaccc gcaaattctg ggggcacatt cttctttact ccgggaacaa aaagttgata 19560 aggatcaccc gcaaattctg ggggcacatt cttctttact ccgggaacaa aaagttgata 19560 aataagttta tccagaatct caagtccggc tatctgatac tagacttaca ccagaatatc 19620 ttcgttaaga atctatccaa gtcagagaaa cagattatta tgacgggggg tttgaaacgt 19680 gagtgggttt ttaaggtaac agtcaaggag accaaagaat ggtataagtt agtcggatac 19740 agtgccctga ttaaggacta attggttgaa ctccggaacc ctaatcctgc cctaggtggt 19800 taggcattat ttgcaatata ttaaagaaaa ctttgaaaat acgaagtttc tattcccagc 19860 tttgtctggt ggccggcatg gtcccagcct cctcgctggc gccggctggg caacattccg 19920 aggggaccgt cccctcggta atggcgaatg ggacgcggcc gatccggctg ctaacaaagc 19980 ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa taactagcat aaccccttgg 20040 ggcctctaaa cgggtcttga ggggtttttt gctgaaagga ggaactatat ccggatgcgg 20100 ccgcgggccc tatggtaccc agcttttgtt ccctttagtg agggttaatt ccgagcttgg 20160 cgtaatcatg gtcatagctg tttcctgtgt gaaattgtta tccgctcaca attccacaca 20220 acataggagc cggaagcata aagtgtaaag cctggggtgc ctaatgagtg aggtaactca 20280 cattaattgc gttgcgctca ctgcccgctt tccagtcggg aaacctgtcg tgccagctgc 20340 attaatgaat cggccaacgc gcggggagag gcggtttgcg tattgggcgc tcttccgctt 20400 cctcgctcac tgactcgctg cgctcggtcg ttcggctgcg gcgagcggta tcagctcact 20460 caaaggcggt aatacggtta tccacagaat caggggataa cgcaggaaag aacatgtgag 20520 caaaaggcca gcaaaaggcc aggaaccgta aaaaggccgc gttgctggcg tttttccata 20580 ggctcggccc ccctgacgag catcacaaaa atcgacgctc aagtcagagg tggcgaaacc 20640 cgacaggact ataaagatac caggcgttcc cccctggaag ctccctcgtg cgctctcctg 20700 ttccgaccct gccgcttacc ggatacctgt ccgcctttct cccttcggga agcgtggcgc 20760 tttctcaatg ctcacgctgt aggtatctca gttcggtgta ggtcgttcgc tccaagctgg 20820 gctgtgtgca cgaacccccc gttcagcccg accgctgcgc cttatccggt aactatcgtc 20880 ttgagtccaa cccggtaaga cacgacttat cgccactggc agcagccact ggtaacagga 20940 ttagcagagc gaggtatgta ggcggtgcta cagagttctt gaagtggtgg cctaactacg 21000 gctacactag aaggacagta tttggtatct gcgctctgct gaagccagtt accttcggaa 21060 aaagagttgg tagctcttga tccggcaaac aaaccaccgc tggtagcggt ggtttttttg 21120 tttgcaagca gcagattacg cgcagaaaaa aaggatctca agaagatcct ttgatctttt 21180 ctacggggtc tgacgctcag tggaacgaaa actcacgtta agggattttg gtcatgagat 21240 tatcaaaaag gatcttcacc tagatccttt taaattaaaa atgaagtttt aaatcaatct 21300 aaagtatata tgagtaaact tggtctgaca gttaccaatg cttaatcagt gaggcaccta 21360 tctcagcgat ctgtctattt cgttcatcca tagttgcctg actgcccgtc gtgtagataa 21420 ctacgatacg ggagggctta ccatctggcc ccagtgctgc aatgataccg cgagacccac 21480 gctcaccggc tccagattta tcagcaataa accagccagc cggaagggcc gagcgcagaa 21540 gtggtcctgc aactttatcc gcctccatcc agtctattaa ttgttgccgg gaagctagag 21600 taagtagttc gccagttaat agtttgcgca acgttgttgc cattgctaca ggcatcgtgg 21660 tgtcacgctc gtcgtttggt atggcttcat tcagctccgg ttcccaacga tcaaggcgag 21720 tgtcacgctc gtcgtttggt atggcttcat tcagctccgg ttcccaacga tcaaggcgag 21720 ttacatgatc ccccatgttg tgaaaaaaag cggttagctc cttcggtcct ccgatcgttg 21780 ttacatgatc ccccatgttg tgaaaaaaag cggttagctc cttcggtcct ccgatcgttg 21780 tcagaagtaa gttggccgca gtgttatcac tcatgcttat ggcagcactg cataattctc 21840 tcagaagtaa gttggccgca gtgttatcac tcatgcttat ggcagcactg cataattctc 21840 ttactgtcat gccatccgta agatgctttt ctgtgactgg tgagtactca accaagtcat 21900 ttactgtcat gccatccgta agatgctttt ctgtgactgg tgagtactca accaagtcat 21900 tctgagaata gtgtatgcgg cgaccgagtt gctcttgccc ggcgtcaata cgggataata 21960 tctgagaata gtgtatgcgg cgaccgagtt gctcttgccc ggcgtcaata cgggataata 21960 ccgcgccaca tagcagaact ttaaaagtgc tcatcattgg aaaacgttct tcggggcgaa 22020 ccgcgccaca tagcagaact ttaaaagtgc tcatcattgg aaaacgttct tcggggcgaa 22020 aactctcaag gatcttaccg ctgttgagat ccagttcgat gtaacccact cgtgcaccca 22080 aactctcaag gatcttaccg ctgttgagat ccagttcgat gtaacccact cgtgcaccca 22080 actgatcttc agcatctttt actttcacca gcgtttctgg gtgagcaaaa acaggaaggc 22140 actgatcttc agcatctttt actttcacca gcgtttctgg gtgagcaaaa acaggaaggc 22140 aaaatgccgc aaaaaaggga ataagggcga cacggaaatg ttgaatactc atactcttcc 22200 aaaatgccgc aaaaaaggga ataagggcga cacggaaatg ttgaatactc atactcttcc 22200 tttttcaata ttattgaagc atttatcagg gttattgtct catgagcgga tacatatttg 22260 tttttcaata ttattgaagc atttatcagg gttattgtct catgagcgga tacatatttg 22260 aatgtattta gaaaaataaa caaatagggg ttccgcgcac atttccccga aaagtgccac 22320 aatgtattta gaaaaataaa caaatagggg ttccgcgcac atttccccga aaagtgccac 22320 ctgaaattgt aaacgttaat attttgttaa aattcgcgtt aaatttttgt taaatcagct 22380 cattttttaa ccaataggcc gaaatcggca aaatccctta taaatcaaaa gaatagaccg 22440 agatagggtt gagtgttgtt ccagtttgga acaagagtcc actattaaag aacgtggact 22500 ccaacgtcaa agggcgaaaa accgtctatc agggcgatgg cccactacgt gaaccatcac 22560 cctaatcaag ttttttgggg tcgaggtgcc gtaaagcact aaatcggaac cctaaaggga 22620 gcccccgatt tagagcttga cggggaaagc cggcgaacgt ggcgagaaag gaagggaaga 22680 aagcgaaagg agcgggcgct agggcgctgg caagtgtagc ggtcacgctg cgcgtaacca 22740 ccacacccgc cgcgcttaat gcgccgctac agggcgcgtc ccattcgcca ttcaggctgc 22800 gcaactgttg ggaagggcga tcggtgcggg cctcttcgct attacgccag ccaccgcggt 22860 g 22861 <210> 15 <211> 18967 <212> DNA <213> Artificial Sequence <220> <223> Plasmid pTM1-MVSchwarz pTM-MVSchw (GenBank: FW366202.1) <400> 15 gcggccgcta atacgactca ctatagggcc aactttgttt ggtctgatga gtccgtgagg 60 acgaaacccg gagtcccggg tcaccaaaca aagttgggta aggatagttc aatcaatgat 120 catcttctag tgcacttagg attcaagatc ctattatcag ggacaagagc aggattaggg 180 atatccgaga tggccacact tttaaggagc ttagcattgt tcaaaagaaa caaggacaaa 240 ccacccatta catcaggatc cggtggagcc atcagaggaa tcaaacacat tattatagta 300 ccaatccctg gagattcctc aattaccact cgatccagac ttctggaccg gttggtgagg 360 ttaattggaa acccggatgt gagcgggccc aaactaacag gggcactaat aggtatatta 420 tccttatttg tggagtctcc aggtcaattg attcagagga tcaccgatga ccctgacgtt 480 agcataaggc tgttagaggt tgtccagagt gaccagtcac aatctggcct taccttcgca 540 tcaagaggta ccaacatgga ggatgaggcg gaccaatact tttcacatga tgatccaatt 600 agtagtgatc aatccaggtt cggatggttc gggaacaagg aaatctcaga tattgaagtg 660 caagaccctg agggattcaa catgattctg ggtaccatcc tagcccaaat ttgggtcttg 720 ctcgcaaagg cggttacggc cccagacacg gcagctgatt cggagctaag aaggtggata 780 aagtacaccc aacaaagaag ggtagttggt gaatttagat tggagagaaa atggttggat 840 gtggtgagga acaggattgc cgaggacctc tccttacgcc gattcatggt cgctctaatc 900 ctggatatca agagaacacc cggaaacaaa cccaggattg ctgaaatgat atgtgacatt 960 gatacatata tcgtagaggc aggattagcc agttttatcc tgactattaa gtttgggata 1020 gaaactatgt atcctgctct tggactgcat gaatttgctg gtgagttatc cacacttgag 1080 tccttgatga acctttacca gcaaatgggg gaaactgcac cctacatggt aatcctggag 1140 aactcaattc agaacaagtt cagtgcagga tcataccctc tgctctggag ctatgccatg 1200 ggagtaggag tggaacttga aaactccatg ggaggtttga actttggccg atcttacttt 1260 gatccagcat attttagatt agggcaagag atggtaagga ggtcagctgg aaaggtcagt 1320 tccacattgg catctgaact cggtatcact gccgaggatg caaggcttgt ttcagagatt 1380 gcaatgcata ctactgagga caagatcagt agagcggttg gacccagaca agcccaagta 1440 tcatttctac acggtgatca aagtgagaat gagctaccga gattgggggg caaggaagat 1500 aggagggtca aacagagtcg aggagaagcc agggagagct acagagaaac cgggcccagc 1560 agagcaagtg atgcgagagc tgcccatctt ccaaccggca cacccctaga cattgacact 1620 gcaacggagt ccagccaaga tccgcaggac agtcgaaggt cagctgacgc cctgcttagg 1680 ctgcaagcca tggcaggaat ctcggaagaa caaggctcag acacggacac ccctatagtg 1740 tacaatgaca gaaatcttct agactaggtg cgagaggccg agggccagaa caacatccgc 1800 ctaccatcca tcattgttat aaaaaactta ggaaccaggt ccacacagcc gccagcccat 1860 caaccatcca ctcccacgat tggagccaat ggcagaagag caggcacgcc atgtcaaaaa 1920 cggactggaa tgcatccggg ctctcaaggc cgagcccatc ggctcactgg ccatcgagga 1980 agctatggca gcatggtcag aaatatcaga caacccagga caggagcgag ccacctgcag 2040 ggaagagaag gcaggcagtt cgggtctcag caaaccatgc ctctcagcaa ttggatcaac 2100 tgaaggcggt gcacctcgca tccgcggtca gggacctgga gagagcgatg acgacgctga 2160 aactttggga atccccccaa gaaatctcca ggcatcaagc actgggttac agtgttatta 2220 cgtttatgat cacagcggtg aagcggttaa gggaatccaa gatgctgact ctatcatggt 2280 tcaatcaggc cttgatggtg atagcaccct ctcaggagga gacaatgaat ctgaaaacag 2340 cgatgtggat attggcgaac ctgataccga gggatatgct atcactgacc ggggatctgc 2400 tcccatctct atggggttca gggcttctga tgttgaaact gcagaaggag gggagatcca 2460 cgagctcctg agactccaat ccagaggcaa caactttccg aagcttggga aaactctcaa 2520 tgttcctccg cccccggacc ccggtagggc cagcacttcc gggacaccca ttaaaaaggg 2580 cacagacgcg agattagcct catttggaac ggagatcgcg tctttattga caggtggtgc 2640 aacccaatgt gctcgaaagt caccctcgga accatcaggg ccaggtgcac ctgcggggaa 2700 tgtccccgag tgtgtgagca atgccgcact gatacaggag tggacacccg aatctggtac 2760 cacaatctcc ccgagatccc agaataatga agaaggggga gactattatg atgatgagct 2820 gttctctgat gtccaagata ttaaaacagc cttggccaaa atacacgagg ataatcagaa 2880 gataatctcc aagctagaat cactgctgtt attgaaggga gaagttgagt caattaagaa 2940 gcagatcaac aggcaaaata tcagcatatc caccctggaa ggacacctct caagcatcat 3000 gatcgccatt cctggacttg ggaaggatcc caacgacccc actgcagatg tcgaaatcaa 3060 tcccgacttg aaacccatca taggcagaga ttcaggccga gcactggccg aagttctcaa 3120 gaaacccgtt gccagccgac aactccaagg aatgacaaat ggacggacca gttccagagg 3180 acagctgctg aaggaatttc agctaaagcc gatcgggaaa aagatgagct cagccgtcgg 3240 gtttgttcct gacaccggcc ctgcatcacg cagtgtaatc cgctccatta taaaatccag 3300 ccggctagag gaggatcgga agcgttacct gatgactctc cttgatgata tcaaaggagc 3360 caatgatctt gccaagttcc accagatgct gatgaagata ataatgaagt agctacagct 3420 caacttacct gccaacccca tgccagtcga cccaactagt acaacctaaa tccattataa 3480 aaaacttagg agcaaagtga ttgcctccca aggtccacaa tgacagagac ctacgacttc 3540 gacaagtcgg catgggacat caaagggtcg atcgctccga tacaacccac cacctacagt 3600 gatggcaggc tggtgcccca ggtcagagtc atagatcctg gtctaggcga caggaaggat 3660 gaatgcttta tgtacatgtt tctgctgggg gttgttgagg acagcgattc cctagggcct 3720 ccaatcgggc gagcatttgg gttcctgccc ttaggtgttg gcagatccac agcaaagccc 3780 gaaaaactcc tcaaagaggc cactgagctt gacatagttg ttagacgtac agcagggctc 3840 aatgaaaaac tggtgttcta caacaacacc ccactaactc tcctcacacc ttggagaaag 3900 gtcctaacaa cagggagtgt cttcaacgca aaccaagtgt gcaatgcggt taatctgata 3960 ccgctcgata ccccgcagag gttccgtgtt gtttatatga gcatcacccg tctttcggat 4020 aacgggtatt acaccgttcc tagaagaatg ctggaattca gatcggtcaa tgcagtggcc 4080 ttcaacctgc tggtgaccct taggattgac aaggcgatag gccctgggaa gatcatcgac 4140 aatacagagc aacttcctga ggcaacattt atggtccaca tcgggaactt caggagaaag 4200 aagagtgaag tctactctgc cgattattgc aaaatgaaaa tcgaaaagat gggcctggtt 4260 tttgcacttg gtgggatagg gggcaccagt cttcacatta gaagcacagg caaaatgagc 4320 aagactctcc atgcacaact cgggttcaag aagaccttat gttacccgct gatggatatc 4380 aatgaagacc ttaatcgatt actctggagg agcagatgca agatagtaag aatccaggca 4440 gttttgcagc catcagttcc tcaagaattc cgcatttacg acgacgtgat cataaatgat 4500 gaccaaggac tattcaaagt tctgtagacc gtagtgccca gcaatgcccg aaaacgaccc 4560 ccctcacaat gacagccaga aggcccggac aaaaaagccc cctccgaaag actccacgga 4620 ccaagcgaga ggccagccag cagccgacgg caagcgcgaa caccaggcgg ccccagcaca 4680 gaacagccct gacacaaggc caccaccagc caccccaatc tgcatcctcc tcgtgggacc 4740 cccgaggacc aacccccaag gctgcccccg atccaaacca ccaaccgcat ccccaccacc 4800 cccgggaaag aaacccccag caattggaag gcccctcccc ctcttcctca acacaagaac 4860 tccacaaccg aaccgcacaa gcgaccgagg tgacccaacc gcaggcatcc gactccctag 4920 acagatcctc tctccccggc aaactaaaca aaacttaggg ccaaggaaca tacacaccca 4980 acagaaccca gaccccggcc cacggcgccg cgcccccaac ccccgacaac cagagggagc 5040 ccccaaccaa tcccgccggc tcccccggtg cccacaggca gggacaccaa cccccgaaca 5100 gacccagcac ccaaccatcg acaatccaag acgggggggc ccccccaaaa aaaggccccc 5160 aggggccgac agccagcacc gcgaggaagc ccacccaccc cacacacgac cacggcaacc 5220 aaaccagaac ccagaccacc ctgggccacc agctcccaga ctcggccatc accccgcaga 5280 aaggaaaggc cacaacccgc gcaccccagc cccgatccgg cggggagcca cccaacccga 5340 accagcaccc aagagcgatc cccgaaggac ccccgaaccg caaaggacat cagtatccca 5400 cagcctctcc aagtcccccg gtctcctcct cttctcgaag ggaccaaaag atcaatccac 5460 cacacccgac gacactcaac tccccacccc taaaggagac accgggaatc ccagaatcaa 5520 gactcatcca atgtccatca tgggtctcaa ggtgaacgtc tctgccatat tcatggcagt 5580 actgttaact ctccaaacac ccaccggtca aatccattgg ggcaatctct ctaagatagg 5640 ggtggtagga ataggaagtg caagctacaa agttatgact cgttccagcc atcaatcatt 5700 agtcataaaa ttaatgccca atataactct cctcaataac tgcacgaggg tagagattgc 5760 agaatacagg agactactga gaacagtttt ggaaccaatt agagatgcac ttaatgcaat 5820 gacccagaat ataagaccgg ttcagagtgt agcttcaagt aggagacaca agagatttgc 5880 gggagtagtc ctggcaggtg cggccctagg cgttgccaca gctgctcaga taacagccgg 5940 cattgcactt caccagtcca tgctgaactc tcaagccatc gacaatctga gagcgagcct 6000 ggaaactact aatcaggcaa ttgagacaat cagacaagca gggcaggaga tgatattggc 6060 tgttcagggt gtccaagact acatcaataa tgagctgata ccgtctatga accaactatc 6120 ttgtgattta atcggccaga agctcgggct caaattgctc agatactata cagaaatcct 6180 gtcattattt ggccccagtt tacgggaccc catatctgcg gagatatcta tccaggcttt 6240 gagctatgcg cttggaggag acatcaataa ggtgttagaa aagctcggat acagtggagg 6300 tgatttactg ggcatcttag agagcggagg aataaaggcc cggataactc acgtcgacac 6360 agagtcctac ttcattgtcc tcagtatagc ctatccgacg ctgtccgaga ttaagggggt 6420 gattgtccac cggctagagg gggtctcgta caacataggc tctcaagagt ggtataccac 6480 tgtgcccaag tatgttgcaa cccaagggta ccttatctcg aattttgatg agtcatcgtg 6540 tactttcatg ccagagggga ctgtgtgcag ccaaaatgcc ttgtacccga tgagtcctct 6600 gctccaagaa tgcctccggg ggtacaccaa gtcctgtgct cgtacactcg tatccgggtc 6660 ttttgggaac cggttcattt tatcacaagg gaacctaata gccaattgtg catcaatcct 6720 ttgcaagtgt tacacaacag gaacgatcat taatcaagac cctgacaaga tcctaacata 6780 cattgctgcc gatcactgcc cggtagtcga ggtgaacggc gtgaccatcc aagtcgggag 6840 caggaggtat ccagacgctg tgtacttgca cagaattgac ctcggtcctc ccatatcatt 6900 ggagaggttg gacgtaggga caaatctggg gaatgcaatt gctaagttgg aggatgccaa 6960 ggaattgttg gagtcatcgg accagatatt gaggagtatg aaaggtttat cgagcactag 7020 catagtctac atcctgattg cagtgtgtct tggagggttg atagggatcc ccgctttaat 7080 atgttgctgc agggggcgtt gtaacaaaaa gggagaacaa gttggtatgt caagaccagg 7140 cctaaagcct gatcttacgg gaacatcaaa atcctatgta aggtcgctct gatcctctac 7200 aactcttgaa acacaaatgt cccacaagtc tcctcttcgt catcaagcaa ccaccgcacc 7260 cagcatcaag cccacctgaa attatctccg gcttccctct ggccgaacaa tatcggtagt 7320 taatcaaaac ttagggtgca agatcatcca caatgtcacc acaacgagac cggataaatg 7380 ccttctacaa agataacccc catcccaagg gaagtaggat agtcattaac agagaacatc 7440 ttatgattga tagaccttat gttttgctgg ctgttctgtt tgtcatgttt ctgagcttga 7500 tcgggttgct agccattgca ggcattagac ttcatcgggc agccatctac accgcagaga 7560 tccataaaag cctcagcacc aatctagatg taactaactc aatcgagcat caggtcaagg 7620 acgtgctgac accactcttc aaaatcatcg gtgatgaagt gggcctgagg acacctcaga 7680 gattcactga cctagtgaaa ttaatctctg acaagattaa attccttaat ccggataggg 7740 agtacgactt cagagatctc acttggtgta tcaacccgcc agagagaatc aaattggatt 7800 atgatcaata ctgtgcagat gtggctgctg aagagctcat gaatgcattg gtgaactcaa 7860 ctctactgga gaccagaaca accaatcagt tcctagctgt ctcaaaggga aactgctcag 7920 ggcccactac aatcagaggt caattctcaa acatgtcgct gtccctgtta gacttgtatt 7980 taggtcgagg ttacaatgtg tcatctatag tcactatgac atcccaggga atgtatgggg 8040 gaacttacct agtggaaaag cctaatctga gcagcaaaag gtcagagttg tcacaactga 8100 gcatgtaccg agtgtttgaa gtaggtgtta tcagaaatcc gggtttgggg gctccggtgt 8160 tccatatgac aaactatctt gagcaaccag tcagtaatga tctcagcaac tgtatggtgg 8220 ctttggggga gctcaaactc gcagcccttt gtcacgggga agattctatc acaattccct 8280 atcagggatc agggaaaggt gtcagcttcc agctcgtcaa gctaggtgtc tggaaatccc 8340 caaccgacat gcaatcctgg gtccccttat caacggatga tccagtgata gacaggcttt 8400 acctctcatc tcacagaggt gttatcgctg acaatcaagc aaaatgggct gtcccgacaa 8460 cacgaacaga tgacaagttg cgaatggaga catgcttcca acaggcgtgt aagggtaaaa 8520 tccaagcact ctgcgagaat cccgagtggg caccattgaa ggataacagg attccttcat 8580 acggggtctt gtctgttgat ctgagtctga cagttgagct taaaatcaaa attgcttcgg 8640 gattcgggcc attgatcaca cacggttcag ggatggacct atacaaatcc aaccacaaca 8700 atgtgtattg gctgactatc ccgccaatga agaacctagc cttaggtgta atcaacacat 8760 tggagtggat accgagattc aaggttagtc cctacctctt cactgtccca attaaggaag 8820 caggcgaaga ctgccatgcc ccaacatacc tacctgcgga ggtggatggt gatgtcaaac 8880 tcagttccaa tctggtgatt ctacctggtc aagatctcca atatgttttg gcaacctacg 8940 atacttccag ggttgaacat gctgtggttt attacgttta cagcccaagc cgctcatttt 9000 cttactttta tccttttagg ttgcctataa agggggtccc catcgaatta caagtggaat 9060 gcttcacatg ggaccaaaaa ctctggtgcc gtcacttctg tgtgcttgcg gactcagaat 9120 ctggtggaca tatcactcac tctgggatgg tgggcatggg agtcagctgc acagtcaccc 9180 gggaagatgg aaccaatcgc agatagggct gctagtgaac caatcacatg atgtcaccca 9240 gacatcaggc atacccacta gtgtgaaata gacatcagaa ttaagaaaaa cgtagggtcc 9300 aagtggttcc ccgttatgga ctcgctatct gtcaaccaga tcttataccc tgaagttcac 9360 ctagatagcc cgatagttac caataagata gtagccatcc tggagtatgc tcgagtccct 9420 cacgcttaca gcctggagga ccctacactg tgtcagaaca tcaagcaccg cctaaaaaac 9480 ggattttcca accaaatgat tataaacaat gtggaagttg ggaatgtcat caagtccaag 9540 cttaggagtt atccggccca ctctcatatt ccatatccaa attgtaatca ggatttattt 9600 aacatagaag acaaagagtc aacgaggaag atccgtgaac tcctcaaaaa ggggaattcg 9660 ctgtactcca aagtcagtga taaggttttc caatgcttaa gggacactaa ctcacggctt 9720 ggcctaggct ccgaattgag ggaggacatc aaggagaaag ttattaactt gggagtttac 9780 atgcacagct cccagtggtt tgagcccttt ctgttttggt ttacagtcaa gactgagatg 9840 aggtcagtga ttaaatcaca aacccatact tgccatagga ggagacacac acctgtattc 9900 ttcactggta gttcagttga gttgctaatc tctcgtgacc ttgttgctat aatcagtaaa 9960 gagtctcaac atgtatatta cctgacattt gaactggttt tgatgtattg tgatgtcata 10020 gaggggaggt taatgacaga gaccgctatg actattgatg ctaggtatac agagcttcta 10080 ggaagagtca gatacatgtg gaaactgata gatggtttct tccctgcact cgggaatcca 10140 acttatcaaa ttgtagccat gctggagcct ctttcacttg cttacctgca gctgagggat 10200 ataacagtag aactcagagg tgctttcctt aaccactgct ttactgaaat acatgatgtt 10260 cttgaccaaa acgggttttc tgatgaaggt acttatcatg agttaactga agctctagat 10320 tacattttca taactgatga catacatctg acaggggaga ttttctcatt tttcagaagt 10380 ttcggccacc ccagacttga agcagtaacg gctgctgaaa atgttaggaa atacatgaat 10440 cagcctaaag tcattgtgta tgagactctg atgaaaggtc atgccatatt ttgtggaatc 10500 ataatcaacg gctatcgtga caggcacgga ggcagttggc caccgctgac cctccccctg 10560 catgctgcag acacaatccg gaatgctcaa gcttcaggtg aagggttaac acatgagcag 10620 tgcgttgata actggaaatc ttttgctgga gtgaaatttg gctgctttat gcctcttagc 10680 ctggatagtg atctgacaat gtacctaaag gacaaggcac ttgctgctct ccaaagggaa 10740 tgggattcag tttacccgaa agagttcctg cgttacgacc ctcccaaggg aaccgggtca 10800 cggaggcttg tagatgtttt ccttaatgat tcgagctttg acccatatga tgtgataatg 10860 cggaggcttg tagatgtttt ccttaatgat tcgagctttg acccatatga tgtgataatg 10860 tatgttgtaa gtggagctta cctccatgac cctgagttca acctgtctta cagcctgaaa 10920 tatgttgtaa gtggagctta cctccatgac cctgagttca acctgtctta cagcctgaaa 10920 gaaaaggaga tcaaggaaac aggtagactt tttgctaaaa tgacttacaa aatgagggca 10980 gaaaaggaga tcaaggaaac aggtagactt tttgctaaaa tgacttacaa aatgagggca 10980 tgccaagtga ttgctgaaaa tctaatctca aacgggattg gcaaatattt taaggacaat 11040 tgccaagtga ttgctgaaaa tctaatctca aacgggattg gcaaatattt taaggacaat 11040 gggatggcca aggatgagca cgatttgact aaggcactcc acactctagc tgtctcagga 11100 gggatggcca aggatgagca cgatttgact aaggcactcc acactctagc tgtctcagga 11100 gtccccaaag atctcaaaga aagtcacagg ggggggccag tcttaaaaac ctactcccga 11160 gtccccaaag atctcaaaga aagtcacagg ggggggccag tcttaaaaac ctactcccga 11160 agcccagtcc acacaagtac caggaacgtg agagcagcaa aagggtttat agggttccct 11220 agcccagtcc acacaagtac caggaacgtg agagcagcaa aagggtttat agggttccct 11220 caagtaattc ggcaggacca agacactgat catccggaga atatggaagc ttacgagaca 11280 caagtaattc ggcaggacca agacactgat catccggaga atatggaagc ttacgagaca 11280 gtcagtgcat ttatcacgac tgatctcaag aagtactgcc ttaattggag atatgagacc 11340 gtcagtgcat ttatcacgac tgatctcaag aagtactgcc ttaattggag atatgagacc 11340 atcagcttgt ttgcacagag gctaaatgag atttacggat tgccctcatt tttccagtgg 11400 atcagcttgt ttgcacagag gctaaatgag atttacggat tgccctcatt tttccagtgg 11400 ctgcataaga ggcttgagac ctctgtcctg tatgtaagtg accctcattg cccccccgac 11460 ctgcataaga ggcttgagac ctctgtcctg tatgtaagtg accctcattg cccccccgac 11460 cttgacgccc atatcccgtt atataaagtc cccaatgatc aaatcttcat taagtaccct 11520 atgggaggta tagaagggta ttgtcagaag ctgtggacca tcagcaccat tccctatcta 11580 tacctggctg cttatgagag cggagtaagg attgcttcgt tagtgcaagg ggacaatcag 11640 accatagccg taacaaaaag ggtacccagc acatggccct acaaccttaa gaaacgggaa 11700 gctgctagag taactagaga ttactttgta attcttaggc aaaggctaca tgatattggc 11760 catcacctca aggcaaatga gacaattgtt tcatcacatt tttttgtcta ttcaaaagga 11820 atatattatg atgggctact tgtgtcccaa tcactcaaga gcatcgcaag atgtgtattc 11880 tggtcagaga ctatagttga tgaaacaagg gcagcatgca gtaatattgc tacaacaatg 11940 gctaaaagca tcgagagagg ttatgaccgt taccttgcat attccctgaa cg...

Claims

1. A nucleic acid construct comprising: (1) A cDNA molecule encoding the full-length antigenomic (+) RNA strand of measles virus MeV of the Edmonston-derived strain; (2) A first heterologous polynucleotide encoding at least the glycoprotein precursor GPC of Lassa virus LASV and the mutant nucleoprotein mNP of LASV, wherein the exonuclease activity of the mutant nucleoprotein mNP is reduced; or (2’) A first heterologous polynucleotide and a second heterologous polynucleotide, wherein the first heterologous polynucleotide encodes at least the glycoprotein precursor GPC of LASV, and the second heterologous polynucleotide encodes at least the zinc-binding protein (Z protein) of LASV, Among them, The first heterologous polynucleotide is operably cloned into an additional transcription unit ATU inserted into the cDNA of the antigenomic (+) RNA of MeV, and The second heterologous polynucleotide is operably cloned into another ATU, which is located at a position different from the position of the first cloned heterologous polynucleotide, The first heterologous polynucleotide is operably cloned into ATU2 located between the P gene and the M gene of MeV, The second heterologous polynucleotide is operably cloned into ATU1 upstream of the N gene inserted into MeV, The heterologous polynucleotide is selected from the following sequences: - SEQ ID No: 2 encoding the GPC protein; - SEQ ID No: 6 encoding the mNP protein; and - SEQ ID No: 8 encoding the Z protein.

2. The nucleic acid construct according to claim 1, wherein, The second heterologous polynucleotide encodes at least one polypeptide different from at least one polypeptide encoded by the first heterologous polynucleotide.

3. The nucleic acid construct according to claim 1, wherein, The heterologous polynucleotide encoding the GPC protein, mNP protein, and / or Z protein is from or derived from the LASV strain Josiah.

4. The nucleic acid construct according to claim 1, wherein, The heterologous polynucleotide is generated or derived from the sequences of Genbank J04324.1 and / or U73034.

2.

5. The nucleic acid construct according to any one of claims 1 to 4, wherein, The mNP protein has a mutated exonuclease domain.

6. The nucleic acid construct according to claim 5, wherein, The encoded mNP protein is the sequence of SEQ ID No:

5.

7. The nucleic acid construct according to claim 5, wherein, The heterologous polynucleotide encoding the mNP protein is SEQ ID No:

6.

8. The nucleic acid construct according to any one of claims 1 to 4, 6 to 7, wherein, The heterologous polynucleotide encoding the GPC protein, mNP protein, and / or Z protein has a codon-optimized open reading frame ORF.

9. The nucleic acid construct according to claim 1, wherein, The heterologous polynucleotide encodes: - The GPC protein of SEQ ID No: 1; and / or - The mNP protein of SEQ ID No: 5; and / or - The Z protein of SEQ ID No:

7.

10. The nucleic acid construct according to claim 1, wherein, The nucleic acid construct comprises the following polynucleotides from the 5'-end to the 3'-end: (a) A polynucleotide encoding the N protein of MeV; (b) A polynucleotide encoding the P protein of MeV; (c) A first heterologous polynucleotide, wherein the first heterologous polynucleotide is operably cloned in an ATU; (d) A polynucleotide encoding the M protein of MeV; (e) A polynucleotide encoding the F protein of MeV; (f) A polynucleotide encoding the H protein of MeV; (g) A polynucleotide encoding the L protein of MeV; The polynucleotide is operably linked in a nucleic acid construct under the control of viral replication and transcription regulatory factors.

11. The nucleic acid construct according to claim 10, wherein, The viral replication and transcription regulatory factors are the MeV leader sequence and the trailer sequence.

12. The nucleic acid construct according to claim 10, wherein, The first heterologous polynucleotide encodes two polypeptides, which are the GPC protein and the mNP protein.

13. The nucleic acid construct according to claim 1, wherein, The nucleic acid construct comprises the following polynucleotides from the 5'-end to the 3'-end: (a) A second heterologous polynucleotide, wherein the second heterologous polynucleotide is operably cloned into ATU1; (b) A polynucleotide encoding the N protein of MeV; (c) A polynucleotide encoding the P protein of MeV; (d) A first heterologous polynucleotide, wherein the first heterologous polynucleotide is operably cloned into ATU2; (e) A polynucleotide encoding the M protein of MeV; (f) A polynucleotide encoding the F protein of MeV; (g) A polynucleotide encoding the H protein of MeV; (h) A polynucleotide encoding the L protein of MeV, The polynucleotide is operably linked in a nucleic acid construct under the control of viral replication and transcription regulatory factors.

14. The nucleic acid construct according to claim 13, wherein, The second heterologous polynucleotide encodes the Z protein.

15. The nucleic acid construct according to claim 13, wherein, The first heterologous polynucleotide encodes a single polypeptide, which is the GPC protein.

16. The nucleic acid construct according to claim 13, wherein, The first heterologous polynucleotide encodes the GPC protein and the mNP protein.

17. The nucleic acid construct according to claim 13, wherein, The viral replication and transcription regulatory factors are the MeV leader sequence and the trailer sequence.

18. The nucleic acid construct according to claim 1, wherein, The first heterologous polynucleotide comprises from the 5'-end to the 3'-end: (a) A nucleic acid encoding the mNP protein of LASV; and (b) A nucleic acid encoding the GPC protein of LASV.

19. The nucleic acid construct according to claim 18, wherein, In (a), for the mNP protein, the nucleic acid is SEQ ID No:

6.

20. The nucleic acid construct according to claim 18, wherein, In (b), the nucleic acid is SEQ ID No:

2.

21. The nucleic acid construct according to claim 1, wherein The first heterologous polynucleotide comprises from the 5'-end to the 3'-end: (a) The nucleic acid of SEQ ID No: 6 encoding the mNP protein; and (b) The nucleic acid of SEQ ID No: 2 encoding the GPC protein.

22. The nucleic acid construct according to claim 1, wherein, The second heterologous polynucleotide encodes the Z protein of LASV, and the first heterologous polynucleotide encodes the GPC protein of LASV.

23. The nucleic acid construct according to claim 22, wherein, The sequence of the second heterologous polynucleotide is the sequence of SEQ ID No: 8, and the sequence of the first heterologous polynucleotide is the sequence of SEQ ID No:

2.

24. The nucleic acid construct according to claim 22, wherein, The first heterologous polynucleotide and the second heterologous polynucleotide are operably cloned into ATUs at different positions in the cDNA molecule of MeV.

25. The nucleic acid construct according to claim 1, wherein The measles virus is an attenuated virus strain selected from the following: Schwarz strain, Zagreb strain, AIK-C strain, Moraten strain, Edmonston seed A strain, Edmonston seed B strain, CAM-70 strain, and TD 97 strain.

26. The nucleic acid construct according to claim 25, wherein, The measles virus is the Schwarz strain.

27. The nucleic acid construct according to claim 1, wherein, The sequence of the first heterologous polynucleotide is SEQ ID No:

2.

28. The nucleic acid construct according to claim 1, wherein, The sequence of the first heterologous polynucleotide consists of SEQ ID No: 2 and SEQ ID No:

6.

29. The nucleic acid construct according to claim 1, wherein, The recombinant cDNA sequence of the nucleic acid construct is selected from: - SEQ ID No: 11 is the construct MeV-mNP-GPC; - SED ID No: 12 is the construct Z-MeV-GPC; and - SEQ ID No: 14 is the construct Z-MeV-mNP-GPC.

30. A transfer plasmid vector comprising the nucleic acid construct according to any one of claims 1 to 29.

31. The transfer plasmid vector according to claim 30, wherein, The transfer plasmid vector comprises or consists of a sequence selected from the following: - SEQ ID No: 11 is the plasmid MeV-mNP-GPC; - SED ID No: 12 is the plasmid Z-MeV-GPC; and - SEQ ID No: 14 is the plasmid Z-MeV-mNP-GPC.

32. Recombinant measles virus, wherein, The virus comprises in its genome the nucleic acid construct according to any one of claims 1 to 29 or the transfer plasmid vector according to claim 30 or 31.

33. Recombinant measles virus, wherein, The genome of the virus consists of the transfer plasmid vector according to claim 30 or 31.

34. The recombinant measles virus according to claim 32 or 33, wherein, The recombinant measles virus expresses at least one polypeptide selected from the GPC protein, mNP protein and Z protein of LASV.

35. A recombinant measles virus according to claim 32 or 33, wherein, The recombinant measles virus expresses at least two polypeptides selected from the GPC protein, mNP protein and Z protein of LASV.

36. The recombinant measles virus according to claim 32 or 33, wherein, The recombinant measles virus expresses the GPC protein and mNP protein of LASV.

37. The recombinant measles virus according to claim 32 or 33, wherein, The recombinant measles virus expresses the GPC protein and Z protein of LASV.

38. The recombinant measles virus according to claim 32, wherein, The recombinant measles virus also expresses at least one of the N protein, P protein, M protein, F protein, H protein and L protein of MeV.

39. The recombinant measles virus according to claim 32, wherein, After a single immunization, the recombinant measles virus elicits a cellular response and / or a humoral response and a cellular response against the GPC protein, NP protein, mNP protein and / or Z protein of LASV.

40. The recombinant measles virus according to claim 39, wherein, The recombinant measles virus elicits a cellular response and / or a humoral response and a cellular response against the N protein, P protein, M protein, F protein, H protein and / or L protein of MeV.

41. The recombinant measles virus according to claim 40, wherein, The cellular response is a T cell response.

42. The recombinant measles virus according to claim 41, wherein, The T cell response is a CD4+ and CD8+ T cell response.

43. A host cell transfected with the nucleic acid construct according to any one of claims 1 to 29 or the transfer plasmid vector according to claim 30 or 31, or infected with the recombinant measles virus according to any one of claims 32 to 42.

44. The host cell according to claim 43, wherein, The host cell is a mammalian cell.

45. An immunogenic composition comprising the recombinant measles virus according to any one of claims 32 to 42 and a pharmaceutically acceptable carrier.

46. The immunogenic composition according to claim 45, wherein, The immunogenic composition is a viral vaccine composition.

47. The immunogenic composition according to claim 45 or 46, wherein, The composition is for a host in need thereof to elicit a protective immune response against Lassa virus by eliciting antibodies against LASV proteins, and / or a cellular response and / or a humoral response and a cellular response against Lassa virus.

48. The immunogenic composition according to claim 47, wherein, The host is a human host.

49. The immunogenic composition according to claim 48, wherein, The human host is a child.

50. The immunogenic composition according to claim 47, wherein, The immunogenic composition elicits a prophylactic immune response against Lassa virus.

51. The immunogenic composition according to claim 45 or 46, wherein, The composition is for a host in need thereof, and elicits a protective immune response against measles virus by eliciting antibodies against measles virus proteins and / or a cellular response and / or a humoral response and a cellular response against measles virus.

52. The immunogenic composition according to claim 51, wherein, The host is a human host.

53. The immunogenic composition according to claim 52, wherein, The human host is a child.

54. The immunogenic composition according to claim 51, wherein, The composition elicits a prophylactic immune response against measles virus.

55. A method for rescuing recombinant Lassa virus-like particles VLP and / or recombinant measles virus, the recombinant Lassa virus-like particles VLP and / or recombinant measles virus expressing at least one polypeptide selected from the GPC protein, mNP protein, and Z protein of LASV, the method comprising: (a) Transfecting cells stably expressing T7 RNA polymerase and measles virus N and P proteins with the nucleic acid construct according to any one of claims 1 to 29 or the transfer plasmid vector according to claim 30 or 31; (b) Maintaining the transfected cells under conditions suitable for producing recombinant measles virus and / or LASV VLP; (c) Infecting cells capable of propagating recombinant measles virus and / or LASV VLP by co-culturing with the transfected cells of step (b); (d) Harvesting recombinant measles virus and / or LASV VLP, the recombinant measles virus expressing at least one of the GPC protein, mNP protein, and / or Z protein of LASV; the LASV VLP expressing at least the Z protein of LASV.

56. The method according to claim 55, wherein, In step (a), the cells are helper cells.

57. The method according to claim 56, wherein, The helper cells are HEK293 helper cells.

58. The method according to claim 55, wherein, The recombinant measles virus expresses the GPC protein and the mNP protein.

59. The method according to claim 55, wherein, The LASV VLP further expresses at least one of the GPC protein and / or mNP protein of LASV.

60. The method according to claim 55, wherein, The LASV VLP expresses the Z protein and the GPC protein. Use of a recombinant measles virus according to any one of claims 32 to 42 for the preparation of a medicament for preventing Lassa virus infection, comprising: A mammal is immunized by injecting the recombinant measles virus according to any one of claims 32 to 42.

62. The application according to claim 61, wherein The injection is subcutaneous injection.

63. The application according to claim 61, wherein The mammal is a human.

64. The application according to claim 61, wherein, The mammal is a child. Use of a recombinant measles virus according to any one of claims 32 to 42 for the preparation of a medicament for treating Lassa virus infection, comprising: A mammal is immunized by injecting the recombinant measles virus according to any one of claims 32 to 42.

66. The application according to claim 65, wherein, The injection is subcutaneous injection.

67. The application according to claim 65, wherein, The mammal is a human.

68. The application according to claim 65, wherein, The mammal is a child.

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