Method for preparing anti-tumor arenavirus and arenavirus mutant

Abstract

The present invention relates to an arenavirus mutant with improved anti-tumor properties, a method for producing the arenavirus mutant, related pharmaceutical compositions, medical uses, methods of treatment, and isolated proteins and nucleic acids.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of priority from German patent application DE 10 2018 215 551.8, filed on September 12, 2018, the contents of which are hereby incorporated by reference in their entirety for all purposes.

[0003] Technical Field and Background

[0004] The present invention relates to methods for preparing anti-tumor arenaviruses, arenavirus mutants, isolated proteins or peptides (especially isolated glycoproteins), arenaviruses and nucleic acids encoding the corresponding proteins or peptides.

[0005] Arenaviruses belong to a family of human-pathogenic polymorphic RNA viruses. Diseases caused by these viruses are considered zoonotic because animals, primarily rodents, are their natural reservoirs. Zoonotic diseases are diseases that can be transmitted from animals to humans and vice versa.

[0006] At least eight arenaviruses are known to cause disease in humans, typically aseptic meningitis and hemorrhagic fever. Known viruses that can cause disease in humans are lymphocytic choriomeningitis virus (LCMV), Guanarito virus (GTOV), Junin virus (JUNV), Lassa virus (LASV), Luyo virus (LUJV), Machupo virus (MACV), Sabie virus (SABV), and Whitewater Arroyo virus (WWAV).

[0007] Mammalian arenaviruses of the genus Arenavirus are divided into two major groups: Old World arenaviruses and New World arenaviruses. These two groups are distinct in terms of their geographical distribution and genetics. Old World arenaviruses, such as lymphocytic choriomeningitis virus, are primarily found in countries in the Eastern Hemisphere (e.g., countries in Europe, Asia, and Africa). In contrast, New World arenaviruses have been found in countries in the Western Hemisphere (e.g., Argentina, Bolivia, Venezuela, Brazil, and the United States).

[0008] Arenaviruses replicate in cells and enter the extracellular space as virus particles (infectious particles). The virus particles are polymorphic, often round, with diameters ranging from 110nm to 130nm, but up to 50nm to 300nm. The capsid of the virus particle is surrounded by an envelope protein composed of a double lipid membrane and a homotrimer of glycoproteins (GP1 and GP2) that protrude into a spike-like structure. GP1 faces outward and binds to cell receptors during infection. GP2 faces the opposite direction and mediates fusion with the cell. The Z-protein is arranged in a ring below the lipid layer. The ribonucleoprotein (RNP) complex within the nucleocapsid is composed of a shorter RNA segment (S segment 3.5kb), a longer RNA segment (L segment 7.2kb), and a nucleoprotein. The L-protein (viral polymerase) is associated with the RNP complex. The L- and S-segments carry genetic information and each encode two proteins. The single-stranded RNA has mixed polarity (i.e., ambiguous), and the sequence (approximately 19-30 bp) at its 3' untranslated end is conserved and is also conserved across viral families. The mRNAs for the nucleoprotein and L-protein are transcribed first, followed by replication and transcription of the mRNAs for the Z-protein and glycoprotein precursors, and finally translation and modification of viral proteins.

[0009] The use of arenaviruses as vaccination vectors is well known. A prominent example is the vaccination virus Candid#1, used against Argentine hemorrhagic fever. It is a vaccination variant of the Junin virus.

[0010] WO 2009 / 083210 A1 discloses the use of replication-defective (i.e., genetically modified) arenavirus particles (virions), particularly for the treatment of tumor diseases such as melanoma, prostate cancer, breast cancer, and lung cancer. The document "Development of replication-defective lymphocytic choriomeningitis virus vectors for the induction of potent CD8+ T cell immunity" (Nature Medicine, vol. 16, no. 3, March 2010, pp. 339-345; doi: 10.1038 / nm.214) mentions potential applications for cancer immunotherapy using such virosomes.

[0011] Furthermore, the use of packaging cells producing retroviral and pseudotyped viral particles with arenavirus glycoproteins for gene therapy of solid tumors is known from WO 2006 / 008074 A1.

[0012] The above-mentioned prior art methods for tumor treatment are based on the use of viral particles that are produced by genetic engineering and are very complex. In addition, for gene therapy treatment, it is usually not possible to fully and therapeutically effectively transduce tumor tissue with genetically engineered viral particles or packaging cells that produce viral particles.

[0013] However, WO 2016 / 166285 A1 discloses an arenavirus for treating and / or preventing tumors, wherein the arenavirus does not contain exogenous genomic RNA. WO 2016 / 166285 A1 also discloses a method for producing an arenavirus having tumor-regressing properties.

[0014] However, there is still a need for specific, in particular therapeutically effective arenaviruses for the treatment and / or prevention of tumors.

[0015] Goals and plans

[0016] The present invention is based on the production of arenaviruses with anti-tumor and / or improved anti-tumor properties. Furthermore, the present invention provides corresponding arenavirus mutants, isolated proteins or peptides (in particular glycoproteins and / or L-proteins), and nucleic acids encoding them.

[0017] The above-mentioned objects are solved by a lymphocytic choriomeningitis virus mutant according to independent claim 1, a method according to independent claim 15, a lymphocytic choriomeningitis virus mutant according to claim 22, a medicament or pharmaceutical composition according to claim 26, an isolated protein or peptide according to claim 28, and an isolated nucleic acid according to claim 29. Preferred embodiments of the method and the lymphocytic choriomeningitis virus mutant are the subject matter of the dependent claims and are defined by the present description. Further aspects of the invention are disclosed in the description. The wording of all claims is hereby incorporated herein by explicit reference to the content of the present description.

[0018] The present invention is based on the surprising discovery that certain mutants of arenaviruses, in particular lymphocytic choriomeningitis virus (LCMV), can have improved anti-tumor activity compared to the wild-type virus.

[0019] Thus, the present invention generally relates to a mutant of lymphocytic choriomeningitis virus, preferably a mutant of strain WE.

[0020] Compared to the wild-type lymphocytic choriomeningitis virus strain WE, the mutant may be able to perform stronger propagation in tumor cells such as H1975 cells, HCC1954 cells, mouse pancreatic cancer cells or human melanoma cells. Compared to the LCMV-WE wild type, the mutant may also be able to induce stronger innate immune activation in vivo. Compared to the LCMV-WE wild type, the mutant may also be able to have a stronger in vivo anti-tumor effect. Compared to the LCMV-WE wild type, the mutant may also be able to increase the amplification of tumor-specific CD8+ T cells. The mutant may also be able to enhance the function of tumor-specific CD8+ T cells. Compared to the LCMV-WE wild type, the mutant may also have a stronger ability to stimulate tumor-specific T cells.

[0021] The lymphocytic choriomeningitis virus mutant of the present invention preferably comprises a nucleic acid encoding a glycoprotein, wherein the glycoprotein comprises at least one mutation at positions corresponding to positions 181 and 185 of the wild-type glycoprotein sequence set forth in SEQ ID NO: 10. Preferred mutations compared to the wild-type glycoprotein sequence set forth in SEQ ID NO: 10 and / or the corresponding protein encoded by the nucleic acid are Arg185→Trp and / or Ile181→Met (e.g., only Arg185→Trp, only Ile181→Met, or both Arg185→Trp and Ile181→Met). While the examples herein demonstrate that the presence of any one of the mutations may be sufficient to provide improved function compared to wild-type lymphocytic choriomeningitis virus, the simultaneous presence of both of the listed mutations further improves LCMV function, and this improvement may be additive or even synergistic. Therefore, in a preferred embodiment, both mutations are present in the LCMV of the present invention.

[0022] Without wishing to be bound by theory, it is further believed that the presence of one or two of the above mutations in the glycoprotein may improve the function of LCMV (e.g., replication or propagation in tumor cells, anti-tumor activity, and / or immune system stimulation, as described above), regardless of the presence of other mutations, particularly other mutations in other genes or proteins of LCMV. This hypothesis is based on the finding that the mutations Arg185→Trp and Ile181→Met described in the glycoprotein remain conserved, while some other mutations appear and disappear during serial passages and / or are not conserved in different mutant strains. This hypothesis is also based on the fact that the glycoprotein of LCMV forms spikes on the viral particle envelope and is therefore believed to play a major role in the ability of the virus to infect tumor cells.

[0023] The LCMV mutant described in the present invention may comprise a nucleic acid encoding a glycoprotein, wherein the glycoprotein has at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, preferably at least about 99.7% sequence identity with the wild-type glycoprotein sequence shown in SEQ ID NO: 10, and / or may comprise the corresponding protein encoded by the nucleic acid.

[0024] The LCMV mutant of the present invention may comprise a nucleic acid encoding a glycoprotein, wherein, compared with the wild-type glycoprotein shown in SEQ ID NO: 10, the glycoprotein comprises the mutations Arg185→Trp and Ile181→Met.

[0025] The LCMV mutants of the present invention may comprise a nucleic acid encoding a glycoprotein, wherein the glycoprotein has a sequence identity of at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.5%, preferably at least about 99.7% to the sequence shown in any one of SEQ ID NOs: 18, 26, 34, 42, 50 and 58, or is preferably identical, and / or may comprise the corresponding protein encoded by the nucleic acid.

[0026] The LCMV mutants of the present invention may comprise a nucleic acid encoding a glycoprotein, wherein the nucleic acid comprises a sequence identity of at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, preferably at least about 99.7% to the sequence shown in SEQ ID NOs: 17, 25, 33, 41, 49 and 57, or is preferably identical, and / or may comprise the corresponding protein encoded by the nucleic acid.

[0027] As mentioned above, it is believed that the LCMV glycoproteins that form the spikes on the viral particle envelope play a major role in the ability of the virus to infect tumor cells. However, other proteins are preferentially presented in LCMV.

[0028] The LCMV mutants of the present invention may comprise a nucleic acid encoding an L-protein having a sequence identity of at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, or preferably at least about 99.7% to the wild-type L-protein sequence shown in SEQ ID NO: 16, and / or may comprise the corresponding protein encoded by the nucleic acid.

[0029] The LCMV mutants of the present invention may comprise a nucleic acid encoding an L-protein, wherein the L-protein has a sequence identity of at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, preferably at least about 99.7%, preferably at least about 99.8%, preferably at least about 99.9% or is identical to the sequence shown in any one of SEQ ID NOs: 24, 32, 40, 48, 56 and 64, and / or may comprise the corresponding protein encoded by the nucleic acid.

[0030] The LCMV mutant of the present invention may comprise a nucleic acid encoding an L-protein, wherein the L-protein comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 mutations at positions corresponding to positions 253, 1512, 1513, 1758, 1995, 2094, 2115, 2141, 2175 and 2185 of the wild-type L-protein sequence shown in SEQ ID NO: 16. Compared to the wild-type L-protein sequence shown in SEQ ID NO: 16, preferred embodiments of mutations at these positions are: Lys253→Arg; Lys1512→Met; Lys1513→Glu; Ser1758→Phe; Phe1995→Ser; Ile2094→Val; Lys2115→Glu; Thr2141→Ala; Arg2175→Lys; Thr2185→Ala, and / or may comprise the corresponding proteins encoded by the nucleic acid. Preferably, the LCMV mutant protein comprises one, two, three, four, or five of the aforementioned mutations.

[0031] The LCMV mutant of the present invention may comprise a nucleic acid encoding an L-protein, wherein the L-protein comprises one of the following mutation groups compared to the wild-type L-protein sequence shown in SEQ ID NO: 16: Ser1758→Phe (corresponding to the mutation of mutant strain P42); Phe1995→Ser, optionally Ile2094→Val, and optionally Thr2141→Ala (corresponding to the mutation of mutant strain P52, which is an oligoclonal for positions 2094 and 2141); Lys1513→Glu, Phe1995→Ser and optionally Arg2175→Lys (corresponding to the mutation of mutant strain P91, which is an oligoclonal for position 2175); Lys253→Arg; Lys 1512→Met; Lys2115→Glu; Thr2185→Ala (corresponding to the mutation of mutant strain P52-1); Phe1995→Ser (corresponding to the mutation of mutant strain P52-1.3); or Lys2115→Glu (corresponding to the mutation of mutant strain P52-2.1), and / or may contain the corresponding protein encoded by the nucleic acid.

[0032] The LCMV mutants of the present invention may comprise a nucleic acid encoding an L-protein, wherein the nucleic acid has a sequence or is preferably complementary to a sequence having at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, preferably at least about 99.7%, preferably at least about 99.8%, preferably at least about 99.9% sequence identity to the sequences shown in SEQ ID NOs: 17, 25, 33, 41, 49 and 57, or is preferably identical to the sequences, and / or may comprise the corresponding protein encoded by the nucleic acid.

[0033] The LCMV mutants of the present invention may comprise a nucleic acid encoding a nucleoprotein, wherein the nucleoprotein has a sequence identity of at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, preferably at least about 99.7% to the nucleoprotein shown in any one of SEQ ID NOs: 12, 20, 28, 36, 44, 52 and 60, or is identical, and / or may comprise the corresponding protein encoded by the nucleic acid.

[0034] The LCMV mutant of the present invention may comprise a nucleic acid encoding a nucleoprotein, wherein the nucleic acid has the following sequence or is preferably complementary to the following sequence: the sequence has at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, preferably at least about 99.7% sequence identity, or is identical to the nucleoprotein represented by any one of SEQ ID NOs: 11, 19, 27, 35, 43, 51 and 59, and / or may comprise the corresponding protein encoded by the nucleic acid.

[0035] The LCMV mutants of the present invention may comprise a nucleic acid encoding a Z-protein, wherein the Z-protein has at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, preferably at least about 99.7% sequence identity to, or is identical to, the sequence shown in any one of SEQ ID NOs: 14, 22, 30, 38, 46, 54 and 62, and / or may comprise the corresponding protein encoded by the nucleic acid.

[0036] The LCMV mutant of the present invention may comprise a nucleic acid encoding a Z-protein, wherein the nucleic acid comprises a sequence that is at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, preferably at least about 99.7% identical to, or is identical to, the sequence shown in any one of SEQ ID NOs: 13, 21, 29, 37, 45, 53 and 61, and / or may comprise the corresponding protein encoded by the nucleic acid.

[0037] The LCMV mutants of the present invention may comprise a glycoprotein, preferably an L protein, preferably an Z protein, and preferably a nucleoprotein, preferably as defined herein. The LCMV mutants of the present invention may comprise a nucleic acid encoding a glycoprotein, preferably an L protein, preferably an Z protein, and preferably a nucleoprotein, preferably as defined herein.

[0038] The LCMV mutants of the present invention may comprise nucleic acids encoding proteins of SEQ ID NOs: 18, 20, 22, and 24, or proteins having at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, or preferably at least about 99.7% sequence identity to these sequences. The glycoprotein may comprise an Ile181→Met mutation. The L-protein may comprise a Ser1758→Phe mutation. The LCMV mutants of the present invention may comprise nucleic acids comprising the sequences of SEQ ID NOs: 17 and 21 and sequences complementary to the sequences of SEQ ID NOs: 19 and 23.

[0039] The LCMV mutants of the present invention may comprise nucleic acids encoding proteins of SEQ ID NOs: 26, 28, 30, and 32, or proteins having at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, or preferably at least about 99.7% sequence identity to these sequences. The glycoprotein may comprise Ile181→Met and Arg185→Trp mutations. The L-protein may comprise the following mutations: Phe1995→Ser, optionally Ile2094→Val, and optionally Thr2141→Ala. The LCMV mutant of the present invention may comprise a nucleic acid comprising the sequences shown in SEQ ID NOs: 25 and 29, and a sequence complementary to the sequences shown in SEQ ID NOs: 27 and 31.

[0040] The LCMV mutants of the present invention may comprise nucleic acids encoding proteins of SEQ ID NOs: 34, 36, 38, and 40, or proteins having at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, or preferably at least about 99.7% sequence identity to these sequences. The glycoprotein may comprise Ile181→Met and Arg185→Trp mutations. The L-protein may comprise the following mutations: Lys1513→Glu, Phe1995→Ser, and optionally Arg2175→Lys. The LCMV mutant of the present invention may comprise a nucleic acid comprising the sequences shown in SEQ ID NOs: 33 and 37, and a sequence complementary to the sequences shown in SEQ ID NOs: 35 and 39.

[0041] The LCMV mutants of the present invention may comprise nucleic acids encoding proteins of SEQ ID NOs: 50, 52, 54, and 56, or proteins having at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, or preferably at least about 99.7% sequence identity to these sequences. The glycoprotein may comprise Ile181→Met and Arg185→Trp mutations. The L-protein may comprise the following mutations: Lys253→Arg; Lys1512→Met; Lys2115→Glu; Thr2185→Ala. The LCMV mutant of the present invention may comprise a nucleic acid comprising the sequences shown in SEQ ID NOs: 41 and 45, and a sequence complementary to the sequences shown in SEQ ID NOs: 43 and 47.

[0042] The LCMV mutants of the present invention may comprise nucleic acids encoding proteins of SEQ ID NOs: 58, 60, 62, and 64, or proteins having at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, or preferably at least about 99.7% sequence identity to these sequences. The glycoprotein may comprise an Arg185→Trp mutation. The L-protein may comprise a Phe1995→Ser mutation. The LCMV mutants of the present invention may comprise nucleic acids comprising the sequences of SEQ ID NOs: 49 and 53 and sequences complementary to the sequences of SEQ ID NOs: 51 and 55.

[0043] The LCMV mutants of the present invention may comprise nucleic acids encoding proteins of SEQ ID NOs: 66, 68, 70, and 72, or proteins having at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, or preferably at least about 99.7% sequence identity to these sequences. The glycoprotein may comprise an Ile181→Met mutation. The L protein may comprise a Lys2115→Glu mutation. The LCMV mutants of the present invention may comprise nucleic acids comprising the sequences of SEQ ID NOs: 57 and 61 and sequences complementary to the sequences of SEQ ID NOs: 59 and 63.

[0044] The LCMV disclosed herein may comprise a nucleic acid encoding the proteins of SEQ ID NOs: 10, 12, 14, and 18, or proteins having at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, preferably at least about 99.7% sequence identity to these sequences. The LCMV disclosed herein may comprise a nucleic acid comprising the sequences set forth in SEQ ID NOs: 10 and 14, and comprising a sequence complementary to the sequences set forth in SEQ ID NOs: 12 and 16.

[0045] The present invention also generally relates to the LCMV disclosed herein, and in particular the LCMV mutants disclosed herein, for use in therapy.

[0046] In particular, when using the LCMV mutants disclosed herein, compared to the use of wild-type lymphocytic choriomeningitis virus strain WE, such use may include stronger propagation of the LCMV mutants in tumors (cells). Compared to the in vivo use of the LCMV-WE wild type, such use may also include inducing stronger innate immune activation. Compared to the use of the LCMV-WE wild type, such use may also include promoting stronger in vivo anti-tumor effects. Compared to the use of the LCMV-WE wild type, such use may also include increasing the amplification of tumor-specific CD8+ T cells. Such use may also include enhancing the function of tumor-specific CD8+ T cells. Compared to the LCMV-WE wild type, such use may also include stimulating tumor-specific T cells to a greater extent.

[0047] The LCMV (mutant) disclosed herein can be used to treat and / or prevent tumors. The tumor can be any tumor disclosed herein. The tumor is preferably selected from carcinoma, melanoma, blastoma, lymphoma and sarcoma.

[0048] According to a first aspect, the present invention relates to a method for preparing antitumor arenaviruses, i.e. tumor-fighting or tumor-repelling arenaviruses (so-called tumor-regressing arenaviruses), in particular arenaviruses having improved antitumor properties, i.e. improved tumor-fighting or tumor-repelling properties, compared to the original arenaviruses.

[0049] The method comprises the following steps:

[0050] a) plating primary tumor cells in a nutrient medium, preferably a liquid nutrient medium, or plating cells of the cell lines H1975, C643 or Tramp-C2 on and / or in a nutrient medium, preferably a liquid nutrient medium;

[0051] b) inoculating plated primary tumor cells with the original arenavirus or inoculating plated cells of the cell lines H1975, C643, or Tramp-C2 with the original arenavirus;

[0052] c) incubating the inoculated primary tumor cells or the inoculated cells of the cell line H1975, C643 or Tramp-C2, i.e. incubating the primary tumor cells and the original arenavirus or the cells of the cell line H1975, C643 or Tramp-C2 and the original arenavirus under conditions suitable for causing infection of at least a portion of the inoculated primary tumor cells or at least a portion of the cells of the inoculated cell line H1975, C643 or Tramp-C2, in particular only a portion of the inoculated primary tumor cells or only a portion of the cells of the inoculated cell line H1975, C643 or Tramp-C2, or all of the inoculated primary tumor cells or all of the inoculated cell line H1975, C643 or Tramp-C2, by the original arenavirus,

[0053] d) extracting a cell culture supernatant containing an arenavirus from an incubated primary tumor cell culture, or extracting a cell culture supernatant containing an arenavirus from a cell culture containing cells of the incubated cell lines H1975, C643 or Tramp-C2,

[0054] The sequence of steps a) to d) is repeated multiple times, wherein when the first repetition of the sequence of steps a) to d) is performed, step b) is performed and the primary tumor cells or cells of the cell line H1975, C643 or Tramp-C2 are inoculated with the cell culture supernatant containing arenavirus or a portion thereof extracted during step d) before the first repetition of the sequence of steps a) to d), and wherein when each further repetition of the sequence of steps a) to d) is performed, step b) is performed and the primary tumor cells or cells of the cell line H1975, C643 or Tramp-C2 are inoculated with the cell culture supernatant containing arenavirus or a portion thereof extracted during step d) of the previous repetition of the sequence of steps a) to d).

[0055] The first execution of the sequence of steps a) to d) can also be referred to as the "first passaging" within the meaning of the present invention. Thus, the first passaging is performed using the original arenavirus as inoculum. Each further passaging is then performed using the arenavirus-containing cell culture supernatant or a portion thereof extracted in step d) of the preceding passaging, preferably the preceding passaging. Starting from the second passaging, the passaging can be referred to as "repeated passaging" within the meaning of the present invention.

[0056] In the context of the present invention, the term "original arenavirus" is understood to refer to the arenavirus used for inoculation (step b)) of primary tumor cells or cells of the cell lines H1975, C643, or Tramp-C2 prior to the first repetition of the sequence of steps a) to d), i.e., prior to the first passage. The "original arenavirus" can refer to a wild-type arenavirus or a mutant thereof, as described in detail below. In particular, the term can refer to an original arenavirus without or with anti-tumor properties.

[0057] In the context of the present invention, the term "wild-type arenavirus" should be understood to mean an arenavirus having a genome that occurs in its genetically normal form in nature.

[0058] In the context of the present invention, the term "primary tumor cells" should be understood as meaning unpassaged or non-passaged tumor cells, i.e. tumor cells isolated directly from tumor tissue or tumor cells isolated directly from tumor tissue that have been passaged for up to 1000 generations, in particular up to 100 generations, preferably up to 10 generations, before performing step a), or primary tumor cells characterized by the presence of different cell clones. In the latter case, heterogeneity can be demonstrated by different protein expression and different DNA sequences (genetic fingerprints).

[0059] In the context of the present invention, the term "cell line H1975" should be understood to mean a cell line isolated from human adenocarcinoma and deposited in ATCC (American Type Culture Collection) under the designation NCI-H1975. And access or deposit number CVCL-1511 cell line.

[0060] In the context of the present invention, the term "cell line C643" should be understood to refer to the cell line isolated from human anaplastic thyroid carcinoma and deposited under the designation C643 and with accession or deposit number CVCL-5969 (ExPASy Cellosaurus).

[0061] In the context of the present invention, the term "cell line Tramp-C2" should be understood as meaning the cell line isolated from murine adenocarcinoma and deposited under the name Tramp-C2 and with accession or deposit number CVCL-3615 (ExPASy Cellosaurus).

[0062] In the context of the present invention, the term "plating out" is understood to mean the inoculation or introduction of primary tumor cells or cells of the cell line H1975, C643 or Tramp-C2 onto and / or into a culture medium, preferably a liquid culture medium. In other words, the term "plating" within the meaning of the present invention is understood to mean the cultivation, in particular the initial cultivation, of primary tumor cells or cells of the cell line H1975, C643 or Tramp-C2 onto and / or into a culture medium, preferably a liquid culture medium.

[0063] The term "lymphocytic choriomeningitis virus WE strain" may refer to the LCMV-WE strain reported by Seiler, P. et al. (Seiler, P., et al., J. Immunol. 162 (8), 4536-4541 (1999)). The term "lymphocytic choriomeningitis virus WE strain" used herein preferably refers to the following LCMV: the LCMV comprises a glycoprotein having a sequence of positions 59 to 265 and 266 to 498 of SEQ ID NO: 10, a nucleoprotein having a sequence of SEQ ID NO: 12; a Z-protein having a sequence of SEQ ID NO: 14; and / or an L-protein having a sequence of SEQ ID NO: 16. The term "lymphocytic choriomeningitis virus WE strain" used herein also preferably refers to an LCMV comprising one or more, preferably two, nucleic acid molecules comprising a sequence of SEQ ID NO: 9, 11, 13 and / or 15 or a sequence complementary thereto.

[0064] In the context of the present invention, the term "arenavirus mutant" or "arenavirus mutant" is understood to mean an arenavirus whose genome and / or proteome has at least one mutation, in particular at least one point mutation, relative to the genome and / or proteome of its wild-type counterpart. Preferably, the term "arenavirus mutant" or "arenavirus mutant" is understood to mean an arenavirus having a protein, in particular a glycoprotein and / or L-protein, which has at least one mutation, preferably in the form of an amino acid substitution, relative to the corresponding protein, in particular a glycoprotein and / or L-protein, of the corresponding wild-type arenavirus.

[0065] Thus, the term "lymphocytic choriomeningitis virus mutant" is understood to mean a mutant of a lymphocytic choriomeningitis virus whose genome and / or proteome has at least one mutation, in particular at least one point mutation, relative to the genome and / or proteome of a wild-type lymphocytic choriomeningitis virus. Preferably, the term "lymphocytic choriomeningitis virus mutant" is understood to mean an arenavirus having a protein, in particular a glycoprotein and / or L-protein, which has at least one mutation, preferably in the form of an amino acid substitution, relative to the corresponding protein, in particular a glycoprotein and / or L-protein, of a wild-type lymphocytic choriomeningitis virus.

[0066] In the context of the present invention, the term "glycoprotein" is to be understood as meaning a macromolecule consisting of a protein (which in certain contexts may also be referred to as a protein part or protein component) and one or more covalently bonded carbohydrate groups (sugar groups), in particular monosaccharide and / or oligosaccharide and / or polysaccharide groups.

[0067] Unless otherwise indicated, in the context of the present invention, the term "repeated passage" or "repeated passaging" is to be understood as a single or repeated process in which primary tumor cells or cells of the cell line H1975, C643 or Tramp-C2 are treated with an arenavirus produced by cells of the primary tumor cells or cell line H1975, C643 or Tramp-C2. For this purpose, a culture medium suitable for cells of the primary tumor cells or cell line H1975, C643 or Tramp-C2 must be used, for example DMEM (Dulbecco's Modified Eagle's Medium) containing 10% fetal calf serum (FKS) and 1% penicillin / streptomycin / glutamine (equivalent to 1 unit / ml penicillin, 100 micrograms / ml streptomycin and 2 mM L-glutamine). Uninfected primary tumor cells or cells of the uninfected cell lines H1975, C643 or Tramp-C2 are preferably plated 0-7 days, in particular 1-7 days, before the inoculation step (step b). Preferably, the culture medium used for cell plating is replaced with fresh culture medium before the inoculation step. In some cases, the culture medium can be extracted 1 minute, 10 minutes or 100 minutes after the inoculation step (step b) and replaced with fresh culture medium. After a period of incubation of 24, 48, 72 or 96 hours, the cell culture supernatant containing the accumulated mutant arenavirus is extracted. A portion of this supernatant is added to new uninfected primary tumor cells or cells of the cell lines H1975, C643 or Tramp-C2.

[0068] As used herein, the term "nucleic acid" can generally refer to either DNA or RNA. DNA and RNA differ, among other things, in their nucleobases. The complementary base to adenine in DNA is thymine, while in RNA it is uracil. For simplicity, the corresponding base to adenine is indicated throughout this document as "t," which, depending on the context, can refer to either thymine (in DNA) or uracil (in RNA).

[0069] The term "encoding" or "encode(s)" as used herein in the context of nucleic acids refers to a nucleic acid having a sequence that can be translated into a specific amino acid sequence encoded by the nucleic acid. The nucleic acid sequence may comprise the sequence of the coding strand or the sequence of a strand complementary to the coding strand.

[0070] "Percent (%) sequence identity" with respect to the sequences disclosed herein is defined as the percentage of amino acid residues or nucleotides in a candidate sequence that are pairwise identical with those in a reference sequence, after the sequences have been aligned and gaps introduced (if necessary to maximize percent sequence identity), and not considering any conservative substitutions as part of the sequence identity. Alignments for determining percent amino acid sequence identity can be accomplished in various ways within the skill in the art, for example, using publicly available computer software such as BLAST, ALIGN, or Megalign (DNASTAR) software. Appropriate parameters for measuring alignments can be determined by those skilled in the art, including any algorithm required to achieve maximum alignment over the full length of the compared sequences. This also applies to the nucleotide sequences disclosed herein. For purposes of determining sequence identity, uracil (e.g., in RNA) can be considered to be identical to thymine (e.g., in DNA).

[0071] The present invention is also based on the surprising discovery that, by passaging primary tumor cells or cells of the cell lines H1975, C643, or Tramp-C2 infected with an arenavirus, it is possible to generate arenaviruses with antitumor properties, in particular, arenaviruses with improved antitumor properties compared to the used arenavirus. The generation of such arenaviruses is based on the fact that the original arenavirus, typically the wild-type arenavirus, has difficulty proliferating in the primary tumor cells or cells of the cell line H1975. Similar restricted proliferation is observed in the cell lines C643 and Tramp-C2. During infection and replication in the primary tumor cells or cells of the cell lines H1975, C643, or Tramp-C2, restricted proliferation triggers enhanced selection or adaptive pressure in the arenavirus. Randomly emerging viral mutants, which are able to proliferate in the primary tumor cells or cells of the cell lines H1975, C643, or Tramp-C2, outcompete the original arenavirus, typically the wild-type arenavirus. Passaging, in particular repeated passaging (multiple repetitions of the sequence of steps a) to d)), preferably results in the enrichment of arenaviruses that have an antitumor effect on primary tumor cells or cells of the cell lines H1975, C643, or Tramp-C2, or that have improved antitumor properties compared to the original arenavirus. The antitumor effect of the arenavirus mutants is based on their ability to better infect cells and replicate within them. This allows them to spread more successfully in the cells used than the original arenaviruses and, in particular, promote enhanced immune activation. Since many tumor cells lack any antiviral factors and therefore exhibit limited viral resistance, the method according to the present invention can be particularly advantageous for producing not only antitumor arenaviruses but also tumor-specific arenaviruses, i.e., antitumor and tumor-specific arenaviruses.

[0072] The primary tumor cells and cells of the cell lines H1975, C643 and Tramp-C2 were identified by the inventors as cells which surprisingly allow only attenuated replication of arenaviruses and which trigger particularly high selection pressure or adaptive stress in arenaviruses during passaging.

[0073] In one embodiment of the present invention, the primary tumor cells have been passaged up to 1000 times, in particular up to 100 times, and preferably up to 10 times, before step a) is performed. In this context, the term "passaging" is understood to mean diluting the cells in a cell culture, thereby taking them into suspension and plating a portion of the cells (e.g., 50%, 10%, or 1%) into a new nutrient medium. The fewer the primary tumor cells are passaged before step a), the more the cells will resemble the characteristics of the patient's tumor cells. In particular, the vast differences (heterogeneity) between individual primary tumor cells in morphology, RNA expression patterns, protein expression, and DNA sequence determine the characteristics of tumor cells in vivo. This advantageously allows the production of arenaviruses that are particularly suitable for the treatment of individual tumor patients, in particular, groups of patients.

[0074] In particular, the primary tumor cells may not have been passaged prior to step a). In other words, unpassaged, i.e., unpassaged, primary tumor cells may be used to perform step a). This forces the original arenavirus or the arenavirus contained in the extracted cell culture supernatant or a portion thereof to adapt to cells that are particularly representative of the patient's tumor cells. This makes it possible to produce arenaviruses specifically suited for the treatment of a particular tumor patient, or in particular a patient group.

[0075] Frequently passaged cells of the cell lines H1975, C643 and Tramp-C2 were identified by the inventors as equally suitable cells, even though they had been passaged in vitro for many years.

[0076] In another embodiment of the present invention, step c) is carried out over a period of time from 1 hour to 1000 hours, in particular from 3 hours to 300 hours, preferably from 12 hours to 96 hours. The time periods disclosed in this paragraph have proven particularly advantageous for the efficient incubation and subsequent infection of inoculated primary tumor cells or inoculated cells of the cell lines H1975, C643 or Tramp-C2 with original arenaviruses or arenaviruses contained in extracted cell culture supernatants or a portion thereof.

[0077] In another embodiment of the invention, step (b) and / or step (c) is carried out at a temperature of 4° C. to 50° C., in particular 20° C. to 42° C., preferably 34° C. to 39° C. The temperature range disclosed in this paragraph has been found to be particularly advantageous for the efficient inoculation and / or incubation (and subsequent infection) of primary tumor cells or cells of the cell lines H1975, C643 or Tramp-C2 with original arenaviruses or arenaviruses contained in extracted cell culture supernatants or a fraction thereof.

[0078] In another embodiment of the present invention, step a) and / or step b) and / or step c) and / or step d) are performed in a nutrient medium, preferably selected from RPMI-1640 (Roswell Memorial Park Institute), DMEM (Dulbecco's Modified Eagle's Medium), and IMDM (Iscove's Modified Dulbecco's Medium). The nutrient medium may further contain serum (0.1-20%), such as fetal bovine serum and / or human serum, and / or amino acids (such as glutamic acid and / or glutamine), and / or antibiotics. The culture medium is capable of culturing primary tumor cells or cells of the cell lines H1975, C643, or Tramp-C2. In particular, the culture medium particularly favors the growth and / or cell division of primary tumor cells or cells of the cell lines H1975, C643, or Tramp-C2. The culture medium mentioned in this paragraph is particularly suitable for culturing primary tumor cells or cells of the cell lines H1975, C643, or Tramp-C2.

[0079] In another embodiment of the present invention, step a) and / or step b) and / or step c) are performed under a carbon dioxide atmosphere (CO atmosphere) of 0% to 20%, in particular 0.1% to 20%, preferably 2% to 10%, and more preferably 4% to 6%. This allows the pH of the nutrient medium used in step a) and / or step b) and / or step c) to remain constant. This allows for efficient plating of primary tumor cells or cells of the cell lines H1975, C643, or Tramp-C2 and / or efficient inoculation and / or incubation (and subsequent infection) of these cells with original arenaviruses or arenaviruses contained in extracted cell culture supernatants or fractions thereof.

[0080] Preferably, step a) and / or step b) and / or step c) are performed in an incubator, by means of which controlled external conditions for cell growth and / or cell division of primary tumor cells or cell lines H1975, C643 or Tramp-C2 can be created.

[0081] In another embodiment of the present invention, the sequence of steps a) to d) is repeated 3 to 1000 times, in particular 10 to 100 times, preferably 20 to 50 times. Multiple repetitions of the sequence of steps a) to d), in particular the number of repetitions disclosed in this paragraph, have been shown to be particularly beneficial for the development of mutations, in particular point mutations, with beneficial anti-tumor properties and, consequently, for the production of anti-tumor arenaviruses.

[0082] In another embodiment of the present invention, before performing step b), the nutrient medium is replaced with a fresh or new nutrient medium. By this step, the infection conditions can be advantageously standardized.

[0083] In another embodiment of the present invention, after step b), the nutrient medium is replaced with a fresh or new culture medium within a time period of 0.1 to 600 minutes, particularly 1 to 30 minutes, preferably 5 to 15 minutes. Due to the limited infection time, this step advantageously increases the selection pressure of infection.

[0084] In another embodiment of the present invention, the nutrient medium is replaced multiple times. For example, before step b), the nutrient medium can be replaced with a fresh or new nutrient medium, and after step b), the latter can be replaced with a fresh or new nutrient medium within a period of 0.1 to 600 minutes, in particular 1 to 30 minutes, and preferably 5 to 15 minutes.

[0085] In another embodiment of the present invention, the primary tumor cells or cells of the cell lines H1975, C643, or Tramp-C2 and / or the original arenavirus and / or the arenavirus contained in the extracted cell culture supernatant or a portion thereof are treated with at least one chemotherapeutic agent before performing step d), in particular before performing step c), in particular before performing step b), and in particular before performing step a). This allows for the simulation of tumor cells that have already been subjected to chemotherapy. This advantageously allows for the production of arenaviruses that are particularly suitable for treating tumor patients who have already been treated with chemotherapy and / or are considered to have exhausted all treatment options.

[0086] In another embodiment of the present invention, the original arenavirus and / or the arenavirus contained in the extracted cell culture supernatant or a portion thereof is treated with at least one chemotherapeutic agent before step b) is performed. This advantageously increases the natural mutation rate of the arenavirus and thus accelerates its adaptation to primary tumor cells or cells of the cell lines H1975, C643, or Tramp-C2.

[0087] The at least one chemotherapeutic agent may be specifically selected from alkylating agents, topoisomerase inhibitors, mitotic inhibitors, antimetabolites, antibiotics, kinase inhibitors, thalidomide derivatives, apoptosis inducers, biotherapeutic agents (such as biological cytostatics), isotope-containing compounds, hormones, hormone antagonists, histone deacetylase inhibitors and other cytostatics.

[0088] The alkylating agent may be selected from the group consisting of oxazophos, N-loss derivatives, alkyl sulfonates, hydrazines, platinum-containing substances, anthracyclines, and mixtures of at least two of the above alkylating agents.

[0089] The oxazophosphamide may, for example, be selected from cyclophosphamide, ifosfamide and mixtures thereof.

[0090] The N-loss derivative may be selected from chlorambucil, melphalan and mixtures thereof.

[0091] The alkyl sulfonate may be, for example, husulfan.

[0092] The hydrazine may, for example, be selected from temozolomide, dacarbazine, procarbazine and a mixture of at least two of the aforementioned hydrazines.

[0093] The platinum-containing substance may, for example, be selected from cisplatin, carboplatin, oxaliplatin, and a mixture of at least two of the platinum-containing substances.

[0094] The anthracycline may, for example, be selected from doxorubicin, daunorubicin, idarubicin, epirubicin, and a mixture of at least two of the anthracyclines.

[0095] The above-mentioned topoisomerase inhibitor may be selected from the group consisting of a topoisomerase I inhibitor, a topoisomerase II inhibitor (etoposide) and a mixture thereof.

[0096] For example, the topoisomerase I inhibitor may be selected from irinotecan, topotecan, and mixtures thereof.

[0097] The topoisomerase II inhibitor may be, for example, etoposide.

[0098] The above-mentioned mitotic inhibitor or antimetabolite can be selected from vinca alkaloids, taxanes, folic acid antagonists, pyrimidine antagonists, purine antagonists, ribonucleotide reductase inhibitors and a mixture of at least two of the above-mentioned mitotic inhibitors or antimetabolites.

[0099] For example, the vinca alkaloids may be selected from vincristine, vinblastine, and mixtures thereof.

[0100] The taxane may be selected from docetaxel, paclitaxel, and mixtures thereof.

[0101] For example, the folate antagonist may be selected from methotrexate, pemetrexed, and mixtures thereof.

[0102] The pyrimidine antagonist may, for example, be selected from cytarabine, 5-fluorouracil, gemcitabine, capecitabine and a mixture of at least two of the pyrimidine antagonists.

[0103] The purine antagonist may, for example, be selected from 5-azacytidine, azathioprine, 6-mercaptopurine, fludarabine and a mixture of at least two of the purine antagonists.

[0104] For example, the ribonucleotide reductase inhibitor can be hydroxyurea.

[0105] The antibiotic may be selected from bleomycin, actinomycin D, mitomycin, and a mixture of at least two of the above antibiotics.

[0106] The above-mentioned kinase inhibitor can be selected from afatinib, alicentinib, axitinib, crizotinib, cobimetinib, dasatinib, dabrafenib, erlotinib, gefitinib, imatinib, ixazomib, lenvatinib, nilotinib, osimertinib, palbociclib, pazopanib, ponatinib, regorafenib, sunitinib, vemurafenib, trametinib, iverolimus and a mixture of at least two of the kinase inhibitors.

[0107] The thalidomide derivative can be selected from lenalidomide, pomalidomide and a mixture thereof.

[0108] The apoptosis inducer can be selected from methoxal, venetoclax and a mixture thereof.

[0109] The biotherapeutic agent may be selected from rituximab, trastuzumab, cetuximab, panitumumab, ipilimumab, penbrezumab, nivolumab, atezolizumab, avelumab, nivolumab, olatumumab, ramucirumab, and a mixture of at least two of the biotherapeutic agents.

[0110] The above-mentioned hormones and / or hormone antagonists can be selected from buserelin, goserelin, leuprorelin, triptorelin, estramustine, tamoxifen, aromatase inhibitors (such as anastrozole), androgen antagonists (such as enzalutamide, flutamide, bicalutamide), progesterone (such as megestrol acetate and medroxyprogesterone acetate), glucocorticoids and a mixture of at least two of the above-mentioned hormones and / or hormone antagonists.

[0111] The above-mentioned other cytostatics can be selected from bexarotene, afatinib, crizotinib, erlotinib, gefitinib, lapatinib, dasatinib, imatinib, nilotinib, ponatinib, regorafenib, sonidegi, hydroxyurea, trametinib, tretininoin, isotretinoin, alitretinoin, MAOP (methyl 5-amino-4-oxopentanoate) and a mixture of at least two of the above-mentioned other cytostatics.

[0112] Furthermore, before performing step d), in particular before performing step c), in particular before performing step b), and in particular before performing step a), the primary tumor cells or cells of the cell lines H1975, C643, or Tramp-C2 and / or the primary arenavirus and / or the arenavirus contained in the extracted cell culture supernatant or a portion thereof can be treated with radiation, in particular selected from ultraviolet (UV) radiation (in particular UVA radiation and / or UVB radiation), alpha radiation, beta radiation, gamma radiation, and X-rays. This advantageously allows for the simulation of tumor cells that have been subjected to therapeutic radiation. This advantageously allows for the production of arenaviruses that can be used, in particular, in patients with tumors who have received radiation therapy.

[0113] Furthermore, before step b), the original arenavirus and / or the arenavirus contained in the extracted cell culture supernatant or a portion thereof is treated with radiation, in particular selected from ultraviolet (UV) radiation (in particular UVA radiation and / or UVB radiation), alpha radiation, beta radiation, gamma radiation and X-rays. This advantageously increases the natural mutation rate of the arenavirus and its adaptability to primary tumor cells or cells of the cell lines H1975, C643 or Tramp-C2.

[0114] In another embodiment of the present invention, primary tumor cells or cells from the cell lines H1975, C643, or Tramp-C2 that are resistant to at least one chemotherapeutic agent are used. For example, primary tumor cells resistant to paclitaxel and / or trametinib can be used. Thus, it is advantageous to simulate tumor cells from patients who develop resistance to at least one chemotherapeutic agent during tumor treatment. The embodiments of the present invention described in this paragraph therefore represent a further possibility for producing potent anti-tumor arenaviruses.

[0115] In another embodiment of the present invention, the primary tumor cells or cells of the cell lines H1975, C643, or Tramp-C2 and / or the original arenavirus and / or the arenavirus contained in the extracted cell culture supernatant or a portion thereof are treated with at least one antiviral compound, in particular interferon-alpha and / or interferon-gamma, before performing step d), in particular before performing step c), in particular before performing step b), and in particular before performing step a). This advantageously forces the original arenavirus or the arenavirus contained in the extracted cell culture supernatant or a portion thereof to adapt to an antiviral environment, thereby producing an anti-tumor arenavirus that also exhibits resistance. From a therapeutic perspective, such an arenavirus is particularly effective because it can also be used to combat tumor tissue that may exhibit viral resistance.

[0116] In addition, the method may further comprise the step e) isolating and / or identifying anti-tumor arenaviruses from the extracted cell culture supernatant or a portion thereof by cloning and / or PCR (polymerase chain reaction) and / or sequencing, in particular arenaviruses having improved anti-tumor properties compared to the original arenaviruses.

[0117] The primary tumor cells used are preferably primary malignant tumor cells, in particular primary cancer cells, primary melanoma cells, primary blastoma cells, primary lymphoma cells or primary sarcoma cells.

[0118] In another embodiment of the present invention, the primary tumor cell is a primary choroidal melanoma cell, a primary anal carcinoma cell, a primary angiosarcoma cell, a primary astrocytoma cell, a primary basal cell carcinoma cell, a primary cervical carcinoma cell, a primary chondrosarcoma cell, a primary choriocarcinoma cell, a primary dermal squamous cell carcinoma cell, a primary small intestinal carcinoma cell, a primary endometrial carcinoma cell, a primary Ewing sarcoma cell, a primary fibrosarcoma cell, a primary gallbladder carcinoma cell, a primary bile duct carcinoma cell, a primary glioblastoma cell, a primary bladder carcinoma cell, a primary ureteral carcinoma cell, a primary urethral carcinoma cell, a primary hepatocellular carcinoma cell, a primary testicular tumor cell, a primary hypopharyngeal carcinoma cell, a primary pituitary carcinoma cell, a primary Kaposi's sarcoma cell, a primary small cell bronchogenic carcinoma cell, a primary colon carcinoma cell, a primary colorectal carcinoma cell, a primary laryngeal carcinoma cell, a primary leiomyosarcoma cell, a primary liposarcoma cell, a primary gastric carcinoma cell, or a primary ureteral carcinoma cell. cells, primary malignant fibrous histiocytoma cells, primary breast cancer cells, primary medulloblastoma cells, primary melanoma cells, primary oral floor cancer cells, primary paranasal sinus cancer cells, primary nasopharyngeal cancer cells, primary adrenocortical cancer cells, primary parathyroid cancer cells, primary neurogenic sarcoma cells, primary non-small cell bronchogenic carcinoma cells, primary renal cancer cells, primary oropharyngeal cancer cells, primary osteosarcoma cells, primary ovarian cancer cells, primary pancreatic tumor cells, primary penile cancer cells, primary pheochromocytoma cells, primary pleural mesothelioma cells, primary prostate cancer cells, primary rectal cancer cells, primary retinoblastoma cells, primary rhabdomyosarcoma cells, primary thyroid cancer cells, primary salivary gland cancer cells, primary esophageal cancer cells, primary tonsil cancer cells, primary vaginal cancer cells, primary vulvar cancer cells, primary Wilms' tumor cells, primary neuroendocrine tumor cells, or primary tongue cancer cells.

[0119] Particularly preferred are primary melanoma cells, primary lung cancer cells, primary pancreatic cancer cells, primary colon cancer cells, primary gastric cancer cells, primary pharyngeal cancer cells, primary laryngeal cancer cells, primary renal cell carcinoma cells, primary ovarian cancer cells, primary endometrial cancer cells, primary thyroid cancer cells, primary prostate cancer cells, primary liver cancer cells or primary sarcoma cells (such as primary neurogenic sarcoma cells, primary osteosarcoma cells or primary rhabdomyosarcoma cells).

[0120] In another embodiment of the present invention, wild-type arenaviruses, so-called wild-type arenaviruses, are used as the original arenaviruses.

[0121] In another embodiment of the present invention, an Old World arenavirus is used as the original arenavirus. Preferably, the Old World arenavirus is selected from the group consisting of Catarina virus, Danfenong virus, Ippy virus (IP-PYV), Kodoko virus, Lassa virus (LASV), Lymphocytic choriomeningitis virus (LCMV), Morogoro virus, Mobala virus (MOBV), Gairo virus, Mopeia virus (MOPV), Pinhal virus, and Skinner Tank virus.

[0122] Lymphocytic choriomeningitis virus, in particular wild-type lymphocytic choriomeningitis virus, is preferably used as the original arenavirus. For example, a strain of lymphocytic choriomeningitis virus, in particular a strain selected from WE, Armstrong, Clone 13, and Docile, can be used as the original arenavirus.

[0123] Particularly preferred is a wild-type lymphocytic choriomeningitis virus, i.e. a wild-type lymphocytic choriomeningitis virus comprising an L-protein comprising or consisting of an amino acid sequence according to SEQ ID NO: 7 and / or a nucleic acid (particularly a ribonucleic acid sequence, preferably an L-ribonucleic acid sequence) comprising or consisting of a nucleic acid sequence complementary to the nucleic acid sequence according to SEQ ID NO: 8.

[0124] In addition, New World arenaviruses can be used as original arenaviruses. The New World arenavirus is preferably selected from the group consisting of Allpahuayo Virus (ALLV), Amapari Virus (AMAV), Bear Canyon Virus (BCNV), Chapare Virus, Cupixi Virus (CPXV), Flexal Virus (FLEV), Guanarito Virus (GTOV), Junin Virus (JUNV), Candid #1, Latino virus (LATV), Machupo virus (MACV), Oliveros virus (OLVV), Parana virus (PARV), Pichinide virus (PICV), Pirital virus (PIRV), Sabia virus (SABV), Takaribo virus (TAKARIBOU virus), and the like. virus (TCRV), Tamiami virus (TAMV), and Whitewater arroyo virus (WWAV).

[0125] Furthermore, arenaviruses without antitumor properties can be used as the original arenaviruses.

[0126] Alternatively, original arenaviruses with anti-tumor properties can be used.

[0127] According to a second aspect, the present invention relates to a lymphocytic choriomeningitis virus mutant, ie a mutant of the lymphocytic choriomeningitis virus.

[0128] The lymphocytic choriomeningitis virus mutant comprises a protein or peptide, in particular a glycoprotein. The protein or peptide comprises a mutation, in particular a point mutation. The mutation, in particular a point mutation, is preferably different from the sequences AJ297484, AJ233196 and the reference sequence LCMV (strain WE-Essen).

[0129] Preferably, the lymphocytic choriomeningitis virus mutant comprises a glycoprotein having at least one mutation, in particular a protein component or protein portion of a glycoprotein, wherein the at least one mutation is an amino acid substitution of isoleucine at position 181 of the glycoprotein by another amino acid, preferably methionine, and / or an amino acid substitution of arginine at position 185 of the glycoprotein by another amino acid, preferably tryptophan.

[0130] Alternatively or in combination, the lymphocytic choriomeningitis virus mutant preferably comprises an L-protein having at least one mutation, wherein the at least one mutation is an amino acid substitution of lysine at position 1513 of the L-protein by another amino acid, preferably glutamic acid, and / or an amino acid substitution of phenylalanine at position 1995 of the L-protein by another amino acid, preferably serine, and / or an amino acid substitution of isoleucine at position 2094 of the L-protein by another amino acid, preferably valine, and / or an amino acid substitution of threonine at position 2141 of the L-protein by another amino acid, preferably alanine, and / or an amino acid substitution of arginine at position 2175 of the L-protein by another amino acid, preferably lysine.

[0131] Alternatively or in combination, the lymphocytic choriomeningitis virus mutant preferably comprises a protein or peptide, in particular a glycoprotein (in particular a protein component or protein portion of a glycoprotein), or an L-protein, comprising or consisting of an amino acid sequence according to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 18, SEQ ID NO: 26, SEQ ID NO: 34, SEQ ID NO: 42, SEQ ID NO: 50, SEQ ID NO: 58, SEQ ID NO: 24, SEQ ID NO: 32, SEQ ID NO: 40, SEQ ID NO: 48, SEQ ID NO: 56 and SEQ ID NO: 64. The amino acid sequence according to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 18, SEQ ID NO: 26, SEQ ID NO: 34, SEQ ID NO: 42, SEQ ID NO: 50 and SEQ ID NO: 58 is preferably the amino acid sequence of a glycoprotein of a lymphocytic choriomeningitis virus mutant. The amino acid sequences of SEQ ID NO: 5, SEQ ID NO: 24, SEQ ID NO: 32, SEQ ID NO: 40, SEQ ID NO: 48, SEQ ID NO: 56 and SEQ ID NO: 64 are preferably the amino acid sequences of the L-protein of the lymphocytic choriomeningitis virus mutant.

[0132] Alternatively or in combination, the lymphocytic choriomeningitis virus mutant preferably comprises a nucleic acid, in particular a ribonucleic acid, encoding a protein or peptide, in particular a glycoprotein or L-protein, comprising or consisting of an amino acid sequence according to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 18, SEQ ID NO: 26, SEQ ID NO: 34, SEQ ID NO: 42, SEQ ID NO: 50, SEQ ID NO: 58, SEQ ID NO: 24, SEQ ID NO: 32, SEQ ID NO: 40, SEQ ID NO: 48, SEQ ID NO: 56 or SEQ ID NO: 64.

[0133] Alternatively or in combination, the lymphocytic choriomeningitis virus mutant preferably comprises a nucleic acid, in particular a ribonucleic acid, which comprises a nucleic acid sequence, in particular a ribonucleic acid sequence, or consists of a nucleic acid sequence, in particular a ribonucleic acid sequence, which is complementary to a nucleic acid sequence according to SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 17, SEQ ID NO: 25, SEQ ID NO: 33, SEQ ID NO: 41, SEQ ID NO: 49, SEQ ID NO: 57, SEQ ID NO: 23, SEQ ID NO: 31, SEQ ID NO: 39, SEQ ID NO: 47, SEQ ID NO: 55 or SEQ ID NO: 56.

[0134] Surprisingly, it was found that the corresponding one or more mutants of the lymphocytic choriomeningitis virus - as described in the previous paragraph - have improved replication capacity in primary tumor cells or cells of the cell line H1975, as well as antitumor properties or improved antitumor properties, in particular compared to wild-type lymphocytic choriomeningitis virus.

[0135] Furthermore, it is preferred that the codon encoding isoleucine at position 181 of the glycoprotein is replaced by another codon, preferably by a codon encoding methionine.

[0136] Furthermore, it is preferred that the codon encoding arginine at position 185 of the glycoprotein is replaced by another codon, preferably by a codon encoding tryptophan.

[0137] Furthermore, it is preferred that the codon encoding histidine at position 155 of the glycoprotein is replaced by another codon, preferably by a codon encoding tyrosine.

[0138] Furthermore, it is preferred that the codon encoding arginine at position 358 of the glycoprotein is replaced by another codon, preferably by a codon encoding lysine.

[0139] Furthermore, it is also preferred that the lymphocytic choriomeningitis virus mutant comprises a nucleic acid comprising a mutation, in particular a ribonucleic acid, preferably an L-ribonucleic acid, wherein the mutation is a substitution of adenine at position 4537 of the nucleic acid (in particular a ribonucleic acid, preferably an L-ribonucleic acid) by a guanine nucleotide.

[0140] Furthermore, it is preferred that the lymphocytic choriomeningitis virus mutant comprises a nucleic acid, in particular a ribonucleic acid, preferably an L-ribonucleic acid, encoding an L-protein comprising a mutation, wherein the mutation is a substitution of lysine at position 1513 of the L-protein by another amino acid, preferably glutamic acid.

[0141] Furthermore, it is preferred that the lymphocytic choriomeningitis virus mutant comprises a nucleic acid, in particular a ribonucleic acid, preferably an L-ribonucleic acid, encoding an L-protein comprising a mutation, wherein the mutation is an amino acid substitution of phenylalanine at position 1995 of the L-protein by another amino acid, preferably serine.

[0142] Furthermore, it is also preferred that the lymphocytic choriomeningitis virus mutant comprises a nucleic acid comprising a mutation, in particular a ribonucleic acid, preferably an L-ribonucleic acid, wherein the mutation is a substitution of a thymine at position 5984 of the nucleic acid (in particular a ribonucleic acid, preferably an L-ribonucleic acid) by a nucleotide of a cytosine.

[0143] Furthermore, it is also preferred that the lymphocytic choriomeningitis virus mutant comprises a nucleic acid, in particular a ribonucleic acid, preferably an L-ribonucleic acid, encoding an L-protein comprising a mutation, wherein the mutation is an amino acid substitution of isoleucine at position 2094 of the L-protein by another amino acid, preferably valine.

[0144] Furthermore, it is also preferred that the lymphocytic choriomeningitis virus mutant comprises a nucleic acid comprising a mutation, in particular a ribonucleic acid, preferably an L-ribonucleic acid, wherein the mutation is a substitution of adenine at position 6280 of the nucleic acid (in particular a ribonucleic acid, preferably an L-ribonucleic acid) by another nucleotide, preferably a guanine nucleotide.

[0145] Furthermore, it is preferred that the lymphocytic choriomeningitis virus mutant comprises a nucleic acid, in particular a ribonucleic acid, preferably an L-ribonucleic acid, encoding an L-protein comprising a mutation, wherein the mutation is an amino acid substitution of threonine at position 2141 of the L-protein by another amino acid, preferably alanine.

[0146] Furthermore, it is also preferred that the lymphocytic choriomeningitis virus mutant comprises a nucleic acid, in particular a ribonucleic acid, preferably an L-ribonucleic acid, comprising a mutation, wherein the mutation is that the adenine at position 6421 of the nucleic acid (in particular a ribonucleic acid, preferably an L-ribonucleic acid) is preferably replaced by another nucleotide, preferably a guanine nucleotide.

[0147] Furthermore, it is also preferred that the lymphocytic choriomeningitis virus mutant comprises a nucleic acid, in particular a ribonucleic acid, preferably an L-ribonucleic acid, encoding an L-protein comprising a mutation, wherein the mutation is an amino acid substitution of arginine at position 2175 of the L-protein, preferably with lysine.

[0148] Furthermore, it is also preferred that the lymphocytic choriomeningitis virus mutant comprises a nucleic acid comprising a mutation, in particular a ribonucleic acid, preferably an L-ribonucleic acid, wherein the mutation is a substitution of the guanine at position 6524 of the nucleic acid (in particular a ribonucleic acid, preferably an L-ribonucleic acid) by the nucleotide adenine.

[0149] In another embodiment of the present invention, the lymphocytic choriomeningitis virus mutant is a lymphocytic choriomeningitis virus mutant for application or use in medicine, including any lymphocytic choriomeningitis virus mutant disclosed herein.

[0150] Preferably, the lymphocytic choriomeningitis virus mutant is a lymphocytic choriomeningitis virus mutant for application or use in treating and / or preventing tumors.

[0151] The tumor is preferably selected from the group consisting of carcinoma, melanoma, blastoma, lymphoma and sarcoma.

[0152] In the context of the present invention, the term "cancer" is understood to mean a malignant tumor of epithelial origin.

[0153] In the context of the present invention, the term "sarcoma" is understood to mean a malignant tumor of mesodermal origin.

[0154] In the context of the present invention, the term "melanoma" is understood to mean a malignant tumor of melanocyte origin.

[0155] In the context of the present invention, the term "lymphoma" is understood to mean a malignant tumor of lymphocyte origin.

[0156] In the context of the present invention, the term "blastoma" is understood to mean a malignant tumor of embryonic origin.

[0157] The cancer is preferably selected from the group consisting of anal cancer, bronchial cancer, lung cancer, endometrial cancer, gallbladder cancer, bladder cancer, hepatocellular carcinoma, testicular cancer, colon cancer, colorectal cancer, rectal cancer, laryngeal cancer, esophageal cancer, stomach cancer, breast cancer, kidney cancer, ovarian cancer, pancreatic cancer, pharyngeal cancer, oropharyngeal cancer, prostate cancer, thyroid cancer and cervical cancer.

[0158] The sarcoma may be selected from the group consisting of angiosarcoma, chondrosarcoma, Ewing's sarcoma, fibrosarcoma, Kaposi's sarcoma, liposarcoma, leiomyosarcoma, malignant fibrous histiocytoma, neurogenic sarcoma, osteosarcoma, and rhabdomyosarcoma.

[0159] Furthermore, the lymphocytic choriomeningitis virus mutants can be prepared or used for local administration, particularly intramuscular, intraperitoneal or subcutaneous administration.

[0160] Alternatively, the lymphocytic choriomeningitis virus mutant can be prepared or used for systemic, particularly intravenous, administration.

[0161] For further features and advantages of the lymphocytic choriomeningitis virus mutants, reference is made entirely to the preceding and following description.

[0162] According to a third aspect, the present invention relates to a mutant of lymphocytic choriomeningitis virus, which comprises a protein or peptide, in particular a glycoprotein or L-protein, or consists of said protein or peptide, which comprises or consists of the amino acid sequence according to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 18, SEQ ID NO: 26, SEQ ID NO: 34, SEQ ID NO: 42, SEQ ID NO: 50, SEQ ID NO: 58, SEQ ID NO: 66, SEQ ID NO: 24, SEQ ID NO: 32, SEQ ID NO: 40, SEQ ID NO: 48, SEQ ID NO: 56 or SEQ ID NO: 64.

[0163] Alternatively or in combination, the lymphocytic choriomeningitis virus mutant comprises a nucleic acid, in particular a ribonucleic acid, wherein the nucleic acid, in particular the ribonucleic acid comprises a nucleic acid sequence, in particular a ribonucleic acid sequence, or consists of a nucleic acid sequence, in particular a ribonucleic acid sequence, which is a nucleic acid sequence according to SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 17, SEQ ID NO: 25, SEQ ID NO: 33, SEQ ID NO: 41, SEQ ID NO: 49, SEQ ID NO: 57, SEQ ID NO: 65, SEQ ID NO: 23, SEQ ID NO: 31, SEQ ID NO: 39, SEQ ID NO: 47, SEQ ID NO: 55 or SEQ ID NO: 63 or is complementary to the nucleic acid sequence.

[0164] Preferably, the lymphocytic choriomeningitis virus mutant is a lymphocytic choriomeningitis virus mutant for application or use in medicine.

[0165] The lymphocytic choriomeningitis virus mutant is particularly preferably a lymphocytic choriomeningitis virus mutant for application or use in the treatment and / or prevention of tumors.

[0166] The tumor is preferably selected from the group consisting of carcinoma, melanoma, blastoma, lymphoma and sarcoma.

[0167] In the context of the present invention, the term "cancer" is understood to mean a malignant tumor of epithelial origin.

[0168] In the context of the present invention, the term "sarcoma" is understood to mean a malignant tumor of mesodermal origin.

[0169] In the context of the present invention, the term "melanoma" is understood to mean a malignant tumor of melanocyte origin.

[0170] In the context of the present invention, the term "lymphoma" is understood to mean a malignant tumor of lymphocyte origin.

[0171] In the context of the present invention, the term "blastoma" is understood to mean a malignant tumor of embryonic origin.

[0172] The cancer is preferably selected from the group consisting of anal cancer, bronchial cancer, lung cancer, endometrial cancer, gallbladder cancer, bladder cancer, hepatocellular carcinoma, testicular cancer, colon cancer, colorectal cancer, rectal cancer, laryngeal cancer, esophageal cancer, stomach cancer, breast cancer, kidney cancer, ovarian cancer, pancreatic cancer, pharyngeal cancer, oropharyngeal cancer, prostate cancer, thyroid cancer and cervical cancer.

[0173] The sarcoma may be selected from the group consisting of angiosarcoma, chondrosarcoma, Ewing's sarcoma, fibrosarcoma, Kaposi's sarcoma, liposarcoma, leiomyosarcoma, malignant fibrous histiocytoma, neurogenic sarcoma, osteosarcoma, and rhabdomyosarcoma.

[0174] Furthermore, the lymphocytic choriomeningitis virus mutants can be prepared or used for local administration, particularly intramuscular, intraperitoneal or subcutaneous administration.

[0175] Alternatively, the lymphocytic choriomeningitis virus mutant can be prepared or used for systemic, particularly intravenous, administration.

[0176] With regard to further features and advantages of the lymphocytic choriomeningitis virus mutant, to avoid repetition, reference is also made to the preceding description, in particular in the context of the second aspect of the invention. The features and advantages described therein, in particular with regard to the lymphocytic choriomeningitis virus mutant, the protein or peptide (in particular glycoprotein) and the nucleic acid (in particular ribonucleic acid), also apply mutatis mutandis to the lymphocytic choriomeningitis virus mutant according to the third aspect of the invention.

[0177] According to a fourth aspect, the present invention relates to a medicament or a pharmaceutical agent comprising a lymphocytic choriomeningitis virus mutant according to the second or third aspect of the invention.

[0178] The drug or agent may also comprise a checkpoint blocker, such as PD-1 (programmed cell death protein 1), and / or an apoptosis modulator, in particular an apoptosis inhibitor such as a SMAC-mimeticum (LCL-161).

[0179] The drug or medicament preferably further comprises a pharmaceutically acceptable carrier. The carrier can be selected from water, aqueous saline solution, aqueous buffer solution, cell culture medium and a combination of at least two of the aforementioned carriers.

[0180] With regard to further features and advantages of the drug or medicament, to avoid repetition, reference is made entirely to the preceding description, in particular in the context of the second and third aspects of the invention. The features and advantages described therein, in particular with regard to the lymphocytic choriomeningitis virus mutant, also apply mutatis mutandis to the drug or medicament according to the fourth aspect of the invention.

[0181] According to a fifth aspect, the present invention relates to a protein or peptide, preferably an isolated protein or peptide, in particular a glycoprotein or L-protein, comprising or consisting of an amino acid sequence according to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 10, SEQ ID NO: 18, SEQ ID NO: 26, SEQ ID NO: 34, SEQ ID NO: 42, SEQ ID NO: 50, SEQ ID NO: 58, SEQ ID NO: 24, SEQ ID NO: 32, SEQ ID NO: 40, SEQ ID NO: 48, SEQ ID NO: 56 or SEQ ID NO: 64. The present invention also relates to isolated proteins or peptides having at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, preferably at least about 99.7% sequence identity to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 10, SEQ ID NO: 18, SEQ ID NO: 26, SEQ ID NO: 34, SEQ ID NO: 42, SEQ ID NO: 50, SEQ ID NO: 58, SEQ ID NO: 24, SEQ ID NO: 32, SEQ ID NO: 40, SEQ ID NO: 48, SEQ ID NO: 56 or SEQ ID NO: 64.

[0182] The amino acid sequences according to SEQ ID NO: 1 and SEQ ID NO: 3 are preferably amino acid sequences of glycoproteins, in particular protein components or protein portions, of mutant lymphocytic choriomeningitis virus. The amino acid sequence according to SEQ ID NO: 5 is preferably the amino acid sequence of the L protein of a mutant lymphocytic choriomeningitis virus. The amino acid sequence according to SEQ ID NO: 7 is preferably the amino acid sequence of the L protein of wild-type lymphocytic choriomeningitis virus.

[0183] The present invention also relates to a protein or peptide, preferably an isolated protein or peptide, in particular a nucleoprotein or Z-protein, comprising or consisting of the amino acid sequence according to SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 14, SEQ ID NO: 22, SEQ ID NO: 30, SEQ ID NO: 38, SEQ ID NO: 46, SEQ ID NO: 54 or SEQ ID NO: 62. The present invention also relates to isolated proteins or peptides having at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, preferably at least about 99.7% sequence identity to SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 44, SEQ ID NO: 52, SEQ ID NO: 60, SEQ ID NO: 14, SEQ ID NO: 22, SEQ ID NO: 30, SEQ ID NO: 38, SEQ ID NO: 46, SEQ ID NO: 54 or SEQ ID NO: 62.

[0184] With regard to further features and advantages of the protein or peptide, to avoid repetition, reference is also made entirely to the preceding description, in particular to the description of the second and third aspects of the invention. The advantages and features described therein, in particular with regard to the protein or peptide, in particular the glycoprotein, also apply mutatis mutandis to the isolated protein or peptide according to the fifth aspect of the invention.

[0185] According to a sixth aspect, the present invention relates to a nucleic acid, preferably an isolated nucleic acid, in particular a ribonucleic acid, comprising a nucleic acid sequence according to SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 17, SEQ ID NO: 25, SEQ ID NO: 33, SEQ ID NO: 41, SEQ ID NO: 49, SEQ ID NO: 57, SEQ ID NO: 23, SEQ ID NO: 31, SEQ ID NO: 39, SEQ ID NO: 47, SEQ ID NO: 55 or SEQ ID NO: 63 or a nucleic acid sequence according to SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 17, SEQ ID NO: 25, SEQ ID NO: 33, SEQ ID NO: 41, SEQ ID NO: 49, SEQ ID NO: 57, SEQ ID NO: 23, SEQ ID NO: 31, SEQ ID NO: 39, SEQ ID NO: 47, SEQ ID NO: 55 or SEQ ID NO: 63. NO: 55 or SEQ ID NO: 63, or consists of a nucleic acid sequence, in particular a ribonucleic acid sequence, complementary to said nucleic acid sequence. The present invention also relates to isolated proteins or peptides having at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4%, preferably at least about 99.5%, preferably at least about 99.6%, preferably at least about 99.7% sequence identity to SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 17, SEQ ID NO: 25, SEQ ID NO: 33, SEQ ID NO: 41, SEQ ID NO: 49, SEQ ID NO: 57, SEQ ID NO: 23, SEQ ID NO: 31, SEQ ID NO: 39, SEQ ID NO: 47, SEQ ID NO: 55 or SEQ ID NO: 63, or the complement of each.

[0186] The present invention also relates to a nucleic acid, preferably an isolated nucleic acid, in particular a ribonucleic acid, comprising or consisting of a nucleic acid sequence according to SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 13, SEQ ID NO: 21, SEQ ID NO: 29, SEQ ID NO: 37, SEQ ID NO: 45, SEQ ID NO: 53 or SEQ ID NO: 61 or a nucleic acid sequence, in particular a ribonucleic acid sequence, complementary to SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 13, SEQ ID NO: 21, SEQ ID NO: 29, SEQ ID NO: 37, SEQ ID NO: 45, SEQ ID NO: 53 or SEQ ID NO: 61. The present invention also relates to isolated proteins or peptides having at least about 95%, preferably at least about 96%, preferably at least about 97%, preferably at least about 98%, preferably at least about 99%, preferably at least about 99.1%, preferably at least about 99.2%, preferably at least about 99.3%, preferably at least about 99.4% sequence identity to SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 51, SEQ ID NO: 59, SEQ ID NO: 13, SEQ ID NO: 21, SEQ ID NO: 29, SEQ ID NO: 37, SEQ ID NO: 45, SEQ ID NO: 53 or SEQ ID NO: 61, or the complement of each.

[0187] The nucleic acid sequences according to SEQ ID NO: 2 and SEQ ID NO: 4 each preferably encode a glycoprotein of the lymphocytic choriomeningitis virus mutant, in particular a protein component or a protein part of a glycoprotein.

[0188] The nucleic acid sequence according to SEQ ID NO: 6 preferably encodes the L-protein of the lymphocytic choriomeningitis virus mutant.

[0189] The nucleic acid sequence of SEQ ID NO: 8 preferably encodes the L-protein of wild-type lymphocytic choriomeningitis virus.

[0190] With regard to further features and advantages of the isolated nucleic acid, reference is made, to avoid repetition, to the preceding description, in particular in the context of the second and third aspects of the invention. The features and advantages described therein, in particular with regard to nucleic acids, in particular ribonucleic acids, also apply mutatis mutandis to the isolated nucleic acid according to the sixth aspect of the invention.

[0191] According to a seventh aspect, the present invention relates to an isolated gene cluster or operon comprising at least one nucleic acid, in particular a ribonucleic acid, according to the fifth aspect of the invention.

[0192] With regard to further features and advantages of the gene cluster or operon, to avoid repetition, reference is also made to the preceding description, in particular in the context of the sixth aspect of the invention. The features and advantages described therein, in particular with regard to nucleic acids, in particular ribonucleic acids, also apply mutatis mutandis to the isolated gene cluster or operon according to the seventh aspect of the invention.

[0193] According to an eighth aspect, the present invention relates to an expression vector comprising at least one nucleic acid according to the sixth aspect of the invention or a gene cluster or operon according to the seventh aspect of the invention.

[0194] With regard to other features and advantages of the expression vector, reference is also made, to avoid repetition, to the present specification, in particular to the description according to the sixth and seventh aspects of the invention. The features and advantages described therein, in particular with regard to nucleic acids and gene clusters or operons, also apply mutatis mutandis to the expression vector according to the eighth aspect of the invention.

[0195] According to a ninth aspect, the present invention relates to an organism, a virus, a vector or a plasmid expressing or comprising a protein or peptide according to the fifth aspect of the invention and / or comprising a nucleic acid, in particular a ribonucleic acid, according to the sixth aspect of the invention.

[0196] The organism may be a host cell, a fungus or a bacterium.

[0197] The host cell may be a eukaryotic or prokaryotic cell. In addition, the host cell may be a cell that can be used to produce an organism and / or a vector and / or a plasmid.

[0198] The bacterium may be, for example, a vaccine vector or another therapeutic bacterium.

[0199] The virus can be, for example, a vaccine vector or another therapeutic virus.

[0200] With regard to the other features and advantages of the host cell, reference is also made, to avoid repetition, to the present specification, in particular to the description of the fifth and sixth aspects of the invention. The features and advantages described therein, in particular with regard to the proteins or peptides (in particular glycoproteins) and nucleic acids (in particular ribonucleic acids), also apply mutatis mutandis to the host cell according to the ninth aspect of the invention.

[0201] Other features and advantages of the present invention are obtained from the following description of preferred embodiments presented by way of example, the corresponding drawings and the claims. The embodiments described below are only intended to provide further description and a better understanding of the present invention and should not be interpreted as limiting.

[0202] The present invention also relates to a pharmaceutical composition comprising LCMV disclosed herein, preferably an LCMV mutant disclosed herein. The composition may further comprise a pharmaceutically acceptable excipient. The pharmaceutical composition may further comprise a checkpoint blocker such as PD-1 (programmed cell death protein 1) and / or a cell apoptosis regulator, particularly an apoptosis inhibitor such as SMAC-mimetics (LCL-161). The pharmaceutical composition may further comprise a pharmaceutically acceptable carrier. The carrier may be selected from water, an aqueous saline solution, an aqueous buffer solution, a cell culture medium, and a combination of at least two of the above carriers.

[0203] The present invention also relates to the use of the LCMV disclosed herein, preferably the LCMV mutant disclosed herein, in the preparation of a medicament. The medicament can be used to treat tumors. The medicament can be the medicament according to the fourth aspect of the present invention.

[0204] The present invention also relates to a method for treating tumors, comprising administering to a subject in need thereof an effective amount of the LCMV disclosed herein, preferably the LCMV mutant disclosed herein, or the agent disclosed herein, or the pharmaceutical composition disclosed herein.

[0205] Unless otherwise indicated, the term "at least" preceding a series of elements should be understood to refer to every element in the series. Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the present invention.

[0206] Wherever used herein, the term "and / or" includes the meaning of "and," "or," and "all or any other combination of the elements connected by the term."

[0207] As used herein, the term "about" or "approximately" means within 20%, preferably within 10%, and more preferably within 5% of a given value or range. However, it also includes the specific number, for example, about 20 includes 20.

[0208] Unless the context requires otherwise, throughout this specification and the claims that follow, the word "comprise" and variations such as "comprises" and "comprising" will be understood to mean the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps. When used herein, the term "comprising" may be replaced by the terms "containing" or "including," or sometimes when used herein, by the term "having."

[0209] When used herein, "consisting of" excludes any element, step, or ingredient not specified in the claimed elements. When used herein, "consisting essentially of" does not exclude materials or steps that do not materially affect the basic and novel characteristics of the claim.

[0210] In each instance herein, any one of the terms "comprising," "consisting essentially of," and "consisting of" may be replaced with either of the other two terms. For example, the term "comprising" is meant to also provide clear support for "consisting essentially of" and "consisting of," the term "consisting essentially of" is meant to also provide clear support for "comprising" and "consisting of," and the term "consisting of" is meant to also provide clear support for "consisting essentially of" and "comprising."

[0211] It should be understood that the present invention is not limited to the specific methods, protocols, materials, reagents and substances described herein, and therefore may vary. The terminology used herein is only for the purpose of describing particular embodiments and is not intended to limit the scope of the present invention, which is limited only by the claims.

[0212] All publications cited throughout this specification (including all patents, patent applications, scientific publications, manufacturer's specifications, instructions, etc.) are hereby incorporated by reference in their entirety. Nothing herein should be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. To the extent that material incorporated by reference is inconsistent or inconsistent with this specification, this specification supersedes any such material. Example

[0213] 1. Methods and Materials

[0214] 1.1 Mice

[0215] For in vivo antitumor analysis, WT animals (C57BL / 6 background) or NOD.SCID mice without an adaptive immune system were used. OT-1 mice were used as transgenic mice carrying an ovalbumin-specific MHC-I restricted T cell receptor.

[0216] 1.2 Cell lines

[0217] MC57 (CVCL_4985) is a murine fibroblast cell line in which the LCMV arenavirus proliferates well. C643 (CVCL_5969) is a human anaplastic thyroid carcinoma cell line. H1975 is a human lung cancer cell line (CVCL_1511, ATCC, CRL-5908, adenocarcinoma). TrampC2 is a murine adenocarcinoma cell line (CVCL_3615). MOPC is a murine oropharyngeal cell line. CMT167 (CVCL_2405) is a murine lung cancer cell line. B16F10-OVA is a murine melanoma cell line (CVCL_0159) expressing ovalbumin as a model antigen. UKE-Mel-13a are primary tumor cells isolated from a human melanoma metastasis that have been passaged less than 100 times. 511950 is a primary tumor cell line isolated from transgenic mouse pancreatic cancer (Mazur PK et al., Nat Med. 2015 Oct;21(10):1163-71.) and has been passaged less than 20 times. 511950R is derived from 511950 cells and has been passaged less than 100 times under treatment with the MEK inhibitor trametinib.

[0218] 1.3 Viruses

[0219] LCMV strain WE was obtained from the laboratory of Professor Zinkemagel (Experimental Immunology, Zurich, Switzerland) and propagated in L929 cells or BHK cells since 2008. Clones LCMV-P42, LCMV-P52 and LCMV-P91 were isolated after different passages and sequenced.

[0220] 1.4 Reagents

[0221] LCL161 (Selleckchem) and anti-PD1 (BioXcell) were tested for their antitumor activities in combination with LCMV and LCMV-P52, respectively.

[0222] 1.5 Detection of LCMV-infected cells by immunofluorescence

[0223] Immunofluorescence was used to detect LCMV in cells. Cells were seeded in 24-well plates, with each well containing a coverslip. Twenty-four hours later, cells were infected with LCMV and stained with a fluorochrome-labeled anti-LCMV-NP antibody (clone VL4). The cells were observed using a fluorescence microscope and photographed with an integrated CCD camera.

[0224] 1.6 Determination of LCMV in the supernatant by plaque assay

[0225] To determine the LCMV production of cells, cells were seeded in 24-well plates and infected with LCMV 24 hours later. Supernatant was extracted 24 hours later. The supernatant was dripped into 24-well plates and MC57 cells (150,000 cells / well) were added. Methylcellulose was added 4 hours later. After another 48 hours, LCMV plaques were analyzed in the cell lawn using anti-LCMV-NP antibody (clone KL53). Plaque counts were performed to determine the number of infectious particles per milliliter in the supernatant.

[0226] 1.7 Virus Passaging

[0227] To adapt the virus to the tumor, different primary tumor cells or tumor cell lines were infected with LCMV-WE. Cells were plated in 24-well plates (approximately 100,000 cells / well in 1 ml of culture medium). After 24 hours, 100 μL of virus at a multiplicity of infection (MOI) of 1 was added. The initial culture medium was removed and fresh culture medium was added between 1-30 minutes (depending on the setup). After 24, 48, or 72 hours, the cell culture supernatant was extracted and frozen for further analysis. 100 microliters (microL) of the extracted supernatant was used to infect newly plated cells. This process was repeated 30-100 times.

[0228] 1.8 Sequencing

[0229] After reverse transcription of the viral RNA, cDNA is amplified using sequence-specific primer pairs (oligonucleotides) in the polymerase chain reaction (PCR). PCR products are purified, sequenced by cycle sequencing (modified Singer method), separated by capillary electrophoresis, and the sequences recorded as electropherograms. The nucleic acid sequence is translated to obtain the protein sequence.

[0230] 1.9 Innate Immune Activation

[0231] The ability of LCMV to activate the innate immune system was determined by the biomarker IFN-α using a murine IFN-α ELISA (Thermofisher).

[0232] 1.10 Adaptive Immune Activation

[0233] The ability of LCMV to activate the adaptive immune system was tested by tetramer staining of activated lymphocytes (NIH, Tetramer Facility).

[0234] 1.11 Tumor Growth and Treatment

[0235] To measure the antitumor effect, 5×10 5 Tumor cells (100 μL) were injected subcutaneously into the right or left flank of C57BL / 6 or NOD.SCID mice (6-12 weeks old). After visible tumors formed, animals were treated and the mean tumor diameter or volume was measured. For the metastasis model, B16F10-OVA cells were injected intravenously.

[0236] 1.12 Isolation and transfer of ovalbumin (tumor)-specific CD8+ T cells

[0237] To analyze tumor-specific CD8 + T cells were transplanted from the spleens of OT-1 mice into C57BL / 6 mice carrying ovalbumin-expressing tumor cells (B16F10-OVA). The spleens were mechanically disrupted and filtered, and each mouse was intravenously injected with 10 7 splenocytes.

[0238] 1.13 Measurement of tumor-specific CD8+ T cells

[0239] To analyze tumor-specific CD8 + To determine the number of T cells, cells from blood were incubated with fluorescent ovalbumin tetramers (four coupled H-2Kb MHC-I molecules carrying the SIINFEKL peptide, NIH Tetramer Facility) and fluorochrome-coupled anti-CD8 antibodies (eBioscience), washed, and analyzed in a flow cytometer. To analyze T cell function, splenocytes were mechanically disrupted and incubated with Brefeldin A with or without SIINFEKL peptide after filtration. After 6 hours, the cells were fixed, permeabilized, and stained with a CD8-specific fluorescent antibody (anti-CD8, eBioscience) and intracellular interferon-γ (anti-interferon-γ, eBioscience). The frequency of IFN-γ-producing cells was analyzed by flow cytometry.

[0240] 1.14 Statistical Analysis

[0241] Means were compared using an unpaired two-sample Student's t-test. Data are presented as mean ± SEM. Statistical significance was determined at p < 0.05.

[0242] 1.15 Generation of LCMV-P42:

[0243] LCMV-WE was passaged 42 times in primary tumor cell culture (UKE-Mel-13a). After 42 passages, functional mutations were detected in the new virus (LCMV-P42). The nucleic acid and amino acid sequences of LCMV-WE and mutant P42 are shown in Figure 2. Figure 25 (A and B) shown.

[0244] 1.16 Generation of LCMV-P91, LCMV-P52, and Their Subclones:

[0245] LCMV-WE was passaged 52 times in the tumor cell line H1975. After 52 passages, mutations I181M and R185W were detected in the glycoprotein of the new virus. In addition, some mutations (quasi-species) that are most likely unrelated and / or oligoclonal were found. The virus was named: "LCMV-P52". In order to determine the stability and importance of mutations I181M and R185W, the supernatant of the P52 generation was passaged 39 more times. The virus derived from this generation was named "LCMV-P91" and still contained mutations I181M and R185W. The virus LCMV-P52 was subcloned by limiting dilution. The cloned virus was named "LCMV-P52.1". Mutations I181M and R185W remained stable. The mutations (quasi-species) that were considered to be unrelated and / or oligoclonal showed some changes. In order to determine the effects of single mutations I181M and R185W, some earlier generations were analyzed. Generation P29 contained viruses with individual I181M and R185W mutations. Viruses from generation P29 were subcloned by limiting dilution. One subclone with the single R185W mutation was designated "LCMV-P52-1.3"; one subclone with the single I181M mutation was designated "LCMV-P52-2.1." The nucleic acid and amino acid sequences of LCMV mutants P52, P92, P52-1, P52-1.3, and P52-2.1 are shown in Table 1. Figure 25 (CG) shows the alignment of nucleic acid and amino acid sequences of LCMV-WE and mutants P42, P52, P92, P52-1, P52-1.3 and P52-2.1. Figure 26 shown in (AH).

[0246] 2. Research

[0247] 2.1 Tumor cell lines MC57, C643, H1975 and primary tumor cell cultures (UKE Mel-13a) were infected with LCMV (strain WE, MOI 1). Replication was measured after 24 hours (n=3).

[0248] This demonstrates that LCMV (strain WE) spreads differently. Compared to the tumor cell line MC57, it spreads less in the cell lines C643 and H1975 and in primary tumor cell cultures (UKE-Mel-13a). The results are presented graphically in Figure 1 Shown in.

[0249] White LCMV-infected cells can be seen in cultures of MC57, C643, H1975, and UKE-Mel-13a. φ = uninfected, LCMV = LCMV-infected.

[0250] 2.2 Infection of the tumor cell line MC57 and primary tumor cell culture 511950 with LCMV (strain WE, MOI 1) (left panel). Tumor cell lines MC57, Tramp-C2, and primary tumor cell cultures (511950 and 511950R) were infected with LCMV (strain WE, MOI 1) (right panel). The number of infectious viral particles in the supernatant was measured after 24 hours.

[0251] This demonstrates that LCMV (strain WE) proliferates less in the Tramp-C2 cell line and primary tumor cell cultures (511950 and 511950R) than in the MC57 tumor cell line. Figure 2 Shown in.

[0252] Figure 2 The following is an example:

[0253] Vertical axis: infectious LCMV particles in the supernatant (PFU / mL),

[0254] Horizontal axis: treatment groups; MC57, Tramp-C2, 511950, 511950R.

[0255] 2.3 LCMV-WE was passaged 42 times in primary tumor cell culture (UKE-Mel-13a). After 42 passages, functional mutations were detected in the new virus (LCMV-P42).

[0256] This demonstrates that primary tumor cells are suitable for modifying arenaviruses through passage. Figure 3 Shown in.

[0257] 2.4 LCMV-WE was passaged 52 times in the tumor cell line H1975. After 52 passages, functional mutations were detected in the new virus LCMV-P52.

[0258] Thus, using H1975 as an example, it was demonstrated that tumor cell lines with reduced LCMV replication (compared to cell line MC57) are suitable for transformation of arenaviruses by passage. Figure 4 Shown in.

[0259] 2.5 LCMV-P52 was passaged 39 times in the tumor cell line H1975. After 39 passages, more functional mutations were detected in the new virus LCMV-P91.

[0260] This proves that H1975 cells can be transformed into arenaviruses through passage. The experimental process is shown in the figure. Figure 5 Shown in.

[0261] 2.6 The cell line H1975 was infected with LCMV-WE and LCMV-P52 (MOI 1). The virus in the supernatant was determined after 12 hours (n=6).

[0262] This demonstrates that LCMV-P52 replicates better than LCMV-WE in H1975 cells. Figure 6 Shown in.

[0263] Figure 6 The following is an example:

[0264] Vertical axis: infectious LCMV particles in the supernatant (PFU / mL),

[0265] Horizontal axis: treatment group; LCMV-WE or LCMV-P52

[0266] 2.7 Dendritic cells derived from mouse bone marrow were infected with LCMV-WE and LCMV-P52 (MOI 1). Virus in the supernatant was determined 24 hours later (n=3).

[0267] This demonstrates that LCMV-P52 replicates better than LCMV-WE in antigen presenting cells. Figure 7 Shown in.

[0268] Figure 7 The following is an example:

[0269] Vertical axis: infectious LCMV particles in the supernatant (PFU / mL),

[0270] Horizontal axis: treatment group; LCMV-WE or LCMV-P52

[0271] 2.8 The tumor cell line H1975 was infected with LCMV-WE or LCMV-P52 (MOI 1). After 24 hours, viral spread was measured by immunofluorescence.

[0272] Thus, using H1975 as an example, it was demonstrated that LCMV-P52 can spread better in tumor cell lines than LCMV-WE. The results are presented in graphical form in Figure 8 Shown in.

[0273] Shown in white are LCMV-infected cells in cultures infected with LCMV-WE or LCMV-P52.

[0274] 2.9 Primary tumor cells (UKE-Mel-13a) were infected with LCMV-WE or LCMV-P52 (MOI 1). Virus spread was measured by immunofluorescence 24 hours later.

[0275] This demonstrates that LCMV-P52 can spread better in primary tumor cells than LCMV-WE. The results are presented in graphical form in Figure 9 Shown in.

[0276] LCMV-infected cells in cultures infected with LCMV-WE or LCMV-P52 appear in white.

[0277] 2.10 Use LCMV-WE or LCMV-P52 (2×10 4 C57BL / 6 mice were infected intravenously with 100 PFU of IFN-α. One day after infection, the activation of the innate immune system was determined by measuring IFN-α in the serum.

[0278] This demonstrates that LCMV-P52 induces stronger innate immune activation than LCMV-WE. Figure 10 Shown in.

[0279] Figure 10 The following is an example:

[0280] Vertical axis: IFN-α concentration (ng / mL serum)

[0281] Abscissa: treatment groups; animals infected with LCMV-WE or LCMV-P52.

[0282] 2.11 Use LCMV-WE or LCMV-P52 (2×10 4 C57BL / 6 mice were infected intravenously with PFU of the virus. Activation of the adaptive immune system (measuring virus-specific CD8+ T cells) was determined by flow cytometry using tetramers.

[0283] This demonstrates that LCMV-P52 induces stronger adaptive immune activation than LCMV-WE. Figure 11 Shown in.

[0284] Figure 11 The following is an example:

[0285] Vertical axis: virus-specific CD8+ T cells (% of total CD8+ T cells in blood),

[0286] Horizontal axis: time (days after infection).

[0287] 2.12 NOD.SCID mice were injected subcutaneously with 5×10 5 H1975 cells (day 7). Mice were additionally treated with 2×10 4 PFULCMV-WE or LCMV-P52 were infected intratumorally (day 0). Tumor growth was analyzed.

[0288] This demonstrates that treatment with LCMV-P52 has a stronger anti-tumor effect than treatment with LCMV-WE. Figure 12 Shown in.

[0289] Figure 12 The following is an example:

[0290] Vertical axis: average tumor diameter (cm),

[0291] Horizontal axis: time (days after LCMV treatment)

[0292] 2.13 Subcutaneous injection of 5×10 5 MOPC cells (day 7). A group of mice were additionally infected intravenously with 2×10 4 PFU LCMV-P52 (n=3, day 0). Tumor growth was analyzed.

[0293] This demonstrates that treatment with LCMV-P52 has a strong anti-tumor effect. The results are presented in the form of a graph. Figure 13 Shown in.

[0294] Figure 13 The following is an example:

[0295] Vertical axis: tumor volume (mm 3 ),

[0296] Horizontal axis: time (days after LCMV treatment)

[0297] 2.14 Subcutaneous injection of 5×10 5 CMT167 cells (day 7). A group of mice were additionally infected intravenously with 2×104 PFU LCMV-P52 (n=3, day 0). Tumor growth was analyzed.

[0298] This demonstrates that treatment with LCMV-P52 has a strong anti-tumor effect. The results are presented in the form of a graph. Figure 14 Shown in.

[0299] Figure 14 The following is an example:

[0300] Vertical axis: tumor volume (mm 3 ),

[0301] Horizontal axis: time (days after LCMV treatment)

[0302] This demonstrates that treatment with LCMV-P52 has a strong anti-tumor effect. The results are presented in graphical form in Figure 15 Shown in.

[0303] Tumor cells in the lung are shown in black; φ = uninfected

[0304] 2.15 C57BL / 6 mice were injected intravenously with 5×10 5 B16F10-OVA cells (day 7). Tumor-specific CD8 isolated from the spleen of OT-1 mice were transplanted + T cells (day 4). A group of mice were additionally treated intravenously with LCMV-P52 (2×10 4 PFU, n=4). On day 9, lungs were removed and photographed.

[0305] = control animals, 4 lungs per group; LCMV-P52 = treated with LCMV-P52, 4 lungs per group.

[0306] 2.16 C57BL / 6 mice were injected intravenously with 5×10 5 B16F10-OVA cells (day 7). Tumor-specific CD8 isolated from the spleen of OT-1 mice were transplanted + T cells (day 4). A group of mice were additionally treated intravenously with LCMV-P52 (2×10 4 PFU, n=4). On day 3, the tumor-specific CD8 + T cell frequency.

[0307] This demonstrates that treatment with LCMV-p52 enhances the expansion of tumor-specific CD8+ T cells. Figure 16 Shown in.

[0308] Figure 16 The following is an example:

[0309] Vertical axis: Frequency of tumor-specific CD8+ T cells in the blood (% of total CD8+ T cells)

[0310] Horizontal axis: treatment group φ = uninfected, LCMV-P52 = treated with LCMV-P52

[0311] 2.17 C57BL / 6 mice were injected intravenously with 5×10 5 B16F10-OVA cells (day 7). Tumor-specific CD8 isolated from the spleen of OT-1 mice were transplanted + T cells (day 4). One group of animals was additionally treated intravenously with LCMV-P52 (2×10 4 PFU, n=4). On day 9, tumor-specific CD8 + Function of T cells.

[0312] This demonstrates that LCMV-p52 treatment enhances the function of tumor-specific CD8+ T cells. Figure 17 Shown in.

[0313] Figure 17 The following is an example:

[0314] Vertical axis: Frequency of tumor-specific CD8+ T cells producing IFN-γ (% of total CD8+ T cells)

[0315] Abscissa: treatment group; φ: not treated with LCMV-P52; LCMV-P52: treated with LCMV-P52; Legend: -: not treated with antigen; +: restimulated with antigen (SIINFEKL peptide).

[0316] 2.18 Subcutaneous injection of 5×10 5 B16F10-OVA cells (day 7). One group of animals did not receive other treatment (n=3). One group of animals was treated with the inhibitor LCL-161 twice a week starting from day 0 (50 mg / kg body weight orally). One group was injected intratumorally with LCMV-WE (2×L0 4 PFU, n=4). One group was treated with LCL-161 and LCMV. Tumor growth was analyzed.

[0317] This demonstrates that treatment with LCMV-WE has a synergistic effect with LCl-161. The results are presented in graphical form. Figure 18 Shown in.

[0318] Figure 18 The following is an example:

[0319] Vertical axis: tumor volume (mm 3 ),

[0320] Horizontal axis: time (days after LCMV administration)

[0321] 2.19 C57BL / 6 mice were injected subcutaneously with 5×10 5 B16F10-OVA cells (day 7). One group of animals did not receive other treatment (n=3). One group of animals was treated with the inhibitor LCL-161 twice a week starting from day 0 (50 mg / kg body weight orally). One group was injected intratumorally with LCMV-WE (2×10 4 PFU, n = 4). One group was treated with LCL-161 and LCMV. The survival of the animals was analyzed.

[0322] It was shown that treatment with LCMV-WE had a synergistic effect with LCl-161. The results are presented in a graphical form. Figure 19 Shown in.

[0323] Figure 19 The following is an example:

[0324] Vertical axis: animal survival rate (%),

[0325] Horizontal axis: time (days after LCMV administration)

[0326] 2.20 C57BL / 6 mice were subcutaneously injected with 5×10 5 B16F10-OVA cells (day 7). One group of animals did not receive other treatments (n=3). One group was injected intratumorally with LCMV-P52 (2×L0 4 PFU, n = 6-8). One group of animals was treated with the checkpoint blocker anti-PD-1 (200 μg intraperitoneally) on days 1, 5, and 8. One group was treated with the checkpoint blocker anti-PD-1 and LCMV-P52. Tumor growth was analyzed.

[0327] This demonstrates that treatment with LCMV-P52 has a synergistic effect with checkpoint blockers (e.g., anti-PD-1). Figure 20 Shown in.

[0328] Figure 20 The following is an example:

[0329] Vertical axis: tumor volume (mm 3 ),

[0330] Horizontal axis: time (days after LCMV treatment)

[0331] The amino acid and nucleic acid sequences mentioned in this specification correspond to the amino acid and nucleic acid sequences disclosed in the sequence listing below.

[0332] 2.21 will be 10 5 H1975 cells were seeded in 24-well plates. After 24 hours, the cells were infected with LCMV-WE, LCMV-P52.1 (I181M, R185W), LCMV-P52-1.3 (R185W), and LCMV-P52-2.1 (I181M) viruses at a multiplicity of infection (MOI) of 0.1. Viruses in the supernatant were analyzed 24 hours later. The results are shown in Table 1. Figure 21 Shown are (mean + SEM, n = 6, * p<0.05, t-test).

[0333] The data indicate that mutations I181M and R185W respectively increase viral propagation in tumor cells.

[0334] Figure 21 The following is an example:

[0335] X-axis: Different viruses

[0336] Y axis: LCMV in supernatant (log 10 PFU / ml)

[0337] 2.22 will be 2.5×10 5 HCC1954 cells were seeded in 24-well plates and then infected with LCMV-WE, LCMV-P52.1 (I181M, R185W), LCMV-P52-1.3 (R185W), and LCMV-P52-2.1 (I181M) at a multiplicity of infection (MOI) of 0.001. Viruses in the supernatant were analyzed 48 hours later. Figure 22 Shown in (error bars show SEM, n = 4, ** p<0.001, ns indicates not significant, one-way ANOVA with Tukey's post-test).

[0338] The data indicate that mutation I181M or mutation 185W increases viral propagation in HCC1954 tumor cells.

[0339] Figure 22 The following is an example:

[0340] X-axis: Different viruses

[0341] Y axis: LCMV in supernatant (log 10 PFU / ml)

[0342] 2.23 Mouse pancreatic cancer cells (511950, 4×10 5 cells), human melanoma cells (UKE118b, 4×10 5 cells) or (UKE1L8c, 4×105 Cells were inoculated into 24-well plates and then infected with LCMV-WE (white bars) or LCMV-P42 (I181M, black bars) at a multiplicity of infection (MOI) of 0.1. Viruses in the supernatant were analyzed 24 hours later. Figure 23 Shown are (mean + SEM, n = 3, * p<0.05, t-test).

[0343] The data indicate that mutation I181M causes increased viral proliferation in tumor cells.

[0344] Figure 23 The following is an example:

[0345] X-axis: Different cell types

[0346] Y axis: LCMV in supernatant (log 10 PFU / ml)

[0347] 2.24 C57BL / 6 mice were infected intravenously with 2×10 4 PFU of LCMV-WE, LCMV-P52.1 (I181M, R185W), LCMV-P52-1.3 (R185W) and LCMV-P52-2.1 (I181M). LCMV-GP33-specific CD8 + The frequency of T cells. Figure 24 Shown are (mean + SEM, n = 6-12, pooled results from four separate experiments, * p<0.05, t-test).

[0348] The data suggest that mutations I181M and R185W increase the ability of LCMV to stimulate specific T cells. The combination of mutations I181M and R185W may have synergistic properties for early T cell stimulation.

[0349] Figure 24 The following is an example:

[0350] X-axis: Different viruses

[0351] Y axis: Tetramer-GP33-bound CD8 + The frequency of T cells (total CD8 + % of T cells).

[0352] The present invention illustratively described herein can be suitably implemented in the absence of one or more elements, one or more limitations not specifically disclosed herein. In addition, the terms and expressions used herein have been used as terms of description rather than as limitations, and when using such terms and expressions, it is not intended to exclude any equivalents of the features shown and described or parts thereof, but it should be recognized that various improvements can be made within the scope of the claimed invention. Therefore, it should be understood that although the present invention has been specifically disclosed by exemplary embodiments and optional features, those skilled in the art may adopt improvements and deformations of the present invention implemented therein disclosed herein, and such improvements and deformations are considered to be within the scope of the present invention.

[0353] The invention is generally and generically described herein. Each of the narrower genus and subgeneric groupings falling within the generic disclosure also form part of the invention. This includes the generic description of the invention with a proviso or negative limitation that removes any subject matter from the genus, regardless of whether the deleted material is specifically recited herein. Sequence Listing <110> Abalos Therapeutics Ltd. <120> Method for preparing anti-tumor arenavirus and arenavirus mutant <130> LC21310004P <150> DE 10 2018 215 551.8 <151> 2018-09-12 <160> 64 <170> PatentIn version 3.5 <210> 1 <211> 498 <212> PRT <213> Lymphocytic choriomeningitis virus <220> <221> MISC_FEATURE <223> Lymphocytic choriomeningitis virus mutant p52 glycoprotein; ssRNA Amphisone-stranded virus; Arenaviridae; Arenavirus; Old World Arenavirus <400> 1 Met Gly Gln Ile Val Thr Met Phe Glu Ala Leu Pro His Ile Ile Asp 1 5 10 15 Glu Val Ile Asn Ile Val Ile Ile Val Leu Ile Ile Ile Thr Ser Ile 20 25 30 Lys Ala Val Tyr Asn Phe Ala Thr Cys Gly Ile Leu Ala Leu Val Ser 35 40 45 Phe Leu Phe Leu Ala Gly Arg Ser Cys Gly Met Tyr Gly Leu Asn Gly 50 55 60 Pro Asp Ile Tyr Lys Gly Val Tyr Gln Phe Lys Ser Val Glu Phe Asp 65 70 75 80 Met Ser His Leu Asn Leu Thr Met Pro Asn Ala Cys Ser Ala Asn Asn 85 90 95 Ser His His Tyr Ile Ser Met Gly Ser Ser Gly Leu Glu Leu Thr Phe 100 105 110 Thr Asn Asp Ser Ile Leu Asn His Asn Phe Cys Asn Leu Thr Ser Ala 115 120 125 Phe Asn Lys Lys Thr Phe Asp His Thr Leu Met Ser Ile Val Ser Ser 130 135 140 Leu His Leu Ser Ile Arg Gly Asn Ser Asn His Lys Ala Val Ser Cys 145 150 155 160 Asp Phe Asn Asn Gly Ile Thr Ile Gln Tyr Asn Leu Ser Phe Ser Asp 165 170 175 Pro Gln Ser Ala Met Ser Gln Cys Trp Thr Phe Arg Gly Arg Val Leu 180 185 190 Asp Met Phe Arg Thr Ala Phe Gly Gly Lys Tyr Met Arg Ser Gly Trp 195 200 205 Gly Trp Ala Gly Ser Asp Gly Lys Thr Thr Trp Cys Ser Gln Thr Ser 210 215 220 Tyr Gln Tyr Leu Ile Ile Gln Asn Arg Thr Trp Glu Asn His Cys Arg 225 230 235 240 Tyr Ala Gly Pro Phe Gly Met Ser Arg Ile Leu Phe Ala Gln Glu Lys 245 250 255 Thr Lys Phe Leu Thr Arg Arg Leu Ala Gly Thr Phe Thr Trp Thr Leu 260 265 270 Ser Asp Ser Ser Gly Val Glu Asn Pro Gly Gly Tyr Cys Leu Thr Lys 275 280 285 Trp Met Ile Leu Ala Ala Glu Leu Lys Cys Phe Gly Asn Thr Ala Val 290 295 300 Ala Lys Cys Asn Val Asn His Asp Glu Glu Phe Cys Asp Met Leu Arg 305 310 315 320 Leu Ile Asp Tyr Asn Lys Ala Ala Leu Ser Lys Phe Lys Gln Asp Val 325 330 335 Glu Ser Ala Leu His Val Phe Lys Thr Thr Val Asn Ser Leu Ile Ser 340 345 350 Asp Gln Leu Leu Met Arg Asn His Leu Arg Asp Leu Met Gly Val Pro 355 360 365 Tyr Cys Asn Tyr Ser Lys Phe Trp Tyr Leu Glu His Ala Lys Thr Gly 370 375 380 Glu Thr Ser Val Pro Lys Cys Trp Leu Val Thr Asn Gly Ser Tyr Leu 385 390 395 400 Asn Glu Thr His Phe Ser Asp Gln Ile Glu Gln Glu Ala Asp Asn Met 405 410 415 Ile Thr Glu Met Leu Arg Lys Asp Tyr Ile Lys Arg Gln Gly Ser Thr 420 425 430 Pro Leu Ala Leu Met Asp Leu Leu Met Phe Ser Thr Ser Ala Tyr Leu 435 440 445 Ile Ser Ile Phe Leu His Leu Val Lys Ile Pro Thr His Arg His Ile 450 455 460 Lys Gly Gly Ser Cys Pro Lys Pro His Arg Leu Thr Asn Lys Gly Ile 465 470 475 480 Cys Ser Cys Gly Ala Phe Lys Val Pro Gly Val Lys Thr Ile Trp Lys 485 490 495 Arg Arg <210> 2 <211> 1497 <212> DNA <213> Lymphocytic choriomeningitis virus <220> <221> MISC_FEATURE <223> Lymphocytic choriomeningitis virus mutant p52 glycoprotein; ssRNA Amphisone-stranded virus; Arenaviridae; Arenavirus; Old World Arenavirus <400> 2 atgggtcaga ttgtgacaat gtttgaggct ttgcctcaca tcattgatga ggtcatcaac 60 attgtcatta ttgtgctcat tataatcacg agcatcaaag ctgtgtacaa tttcgccacc 120 tgtgggatat tagcactggt cagcttcctt tttttggctg gtaggtcctg tggcatgtac 180 ggccttaatg gtcccgacat ctataaaggg gtttaccagt tcaaatcagt ggagtttgat 240 atgtctcact taaatctgac gatgcccaat gcgtgctcag ccaacaactc tcatcactac 300 atcagtatgg gaagctctgg actggagcta actttcacta acgactccat ccttaatcac 360 aatttttgca acttaacctc cgctttcaac aaaaagactt ttgaccatac actcatgagt 420 atagtctcga gtctgcacct cagtattaga gggaattcca accacaaagc agtgtcttgt 480 gattttaaca atggcatcac cattcaatac aacttgtcat ttcggaccc acagagcgct 540 atgagccagt gttggacttt cagaggtaga gtcttggaca tgtttagac tgcctttgga 600 ggaaaataca tgagagtgg ctggggctgg gcaggttcag atggcagac cacttggtgc 660 agccaaacaa gctatcagta cctaatcata siaaacagga cttgggaaaa ccactgtaga 720 tatgcaggcc cttttgggat gtctagaatc ctctttgctc aggaaagac aaagtttctc 780 actaggagac ttgcaggcac attcacctgg accctgtcag actcctcagg agtagaaaat 840 ccaggtggtt attgcctgac caatggatg atccttgctg cagagctca atgttttggg 900 atacagctg ttgcaaatg taatgtcaat catgatgaag agttctgtga catgctacga 960 ctaattgatt acaaaggc cgccctgagt aagttcaagc aagatgtaga gtctgccttg 1020 catgtattca aaaacagt aaattctctg atttccgatc agctgttgat gaggaatcat 1080 ctaagagatc taatgggggt accatactgt aattactcaa agttctggta tctggaacat 1140 gctaagactg gtgagactag tgtacccaag tgctggcttg tcactaatgg ctcctacttg 1200 aatgagaccc actttagtga tcaaatcgaa caagaagcag ataacatgat cacagagatg 1260 ttgaggaagg actacataaa aagacaaggg agtactcctt tagccttaat ggatcttttg 1320 atgttttcaa catcagcata tctaatcagc atctttctgc atcttgtgaa gataccaaca 1380 catagacaca taaagggcgg ttcatgtcca aagccacaccc gcttgaccaa caaggggatc 1440 tgtagttgtg gtgcattcaa ggtgcctggt gtaaaaacta tctggaaaag acgctga 1497 <210> 3 <211> 498 <212> PRT <213> Lymphocytic choriomeningitis virus <220> <221> MISC_FEATURE <223> Lymphocytic choriomeningitis virus mutant p42 glycoprotein; ssRNA Amphisone-stranded virus; Arenaviridae; Arenavirus; Old World Arenavirus <400> 3 Met Gly Gln Ile Val Thr Met Phe Glu Ala Leu Pro His Ile Ile Asp 1 5 10 15 Glu Val Ile Asn Ile Val Ile Ile Val Leu Ile Ile Ile Thr Ser Ile 20 25 30 Lys Ala Val Tyr Asn Phe Ala Thr Cys Gly Ile Leu Ala Leu Val Ser 35 40 45 Phe Leu Phe Leu Ala Gly Arg Ser Cys Gly Met Tyr Gly Leu Asn Gly 50 55 60 Pro Asp Ile Tyr Lys Gly Val Tyr Gln Phe Lys Ser Val Glu Phe Asp 65 70 75 80 Met Ser His Leu Asn Leu Thr Met Pro Asn Ala Cys Ser Ala Asn Asn 85 90 95 Ser His His Tyr Ile Ser Met Gly Ser Ser Gly Leu Glu Leu Thr Phe 100 105 110 Thr Asn Asp Ser Ile Leu Asn His Asn Phe Cys Asn Leu Thr Ser Ala 115 120 125 Phe Asn Lys Lys Thr Phe Asp His Thr Leu Met Ser Ile Val Ser Ser 130 135 140 Leu His Leu Ser Ile Arg Gly Asn Ser Asn His Lys Ala Val Ser Cys 145 150 155 160 Asp Phe Asn Asn Gly Ile Thr Ile Gln Tyr Asn Leu Ser Phe Ser Asp 165 170 175 Pro Gln Ser Ala Met Ser Gln Cys Arg Thr Phe Arg Gly Arg Val Leu 180 185 190 Asp Met Phe Arg Thr Ala Phe Gly Gly Lys Tyr Met Arg Ser Gly Trp 195 200 205 Gly Trp Ala Gly Ser Asp Gly Lys Thr Thr Trp Cys Ser Gln Thr Ser 210 215 220 Tyr Gln Tyr Leu Ile Ile Gln Asn Arg Thr Trp Glu Asn His Cys Arg 225 230 235 240 Tyr Ala Gly Pro Phe Gly Met Ser Arg Ile Leu Phe Ala Gln Glu Lys 245 250 255 Thr Lys Phe Leu Thr Arg Arg Leu Ala Gly Thr Phe Thr Trp Thr Leu 260 265 270 Ser Asp Ser Ser Gly Val Glu Asn Pro Gly Gly Tyr Cys Leu Thr Lys 275 280 285 Trp Met Ile Leu Ala Ala Glu Leu Lys Cys Phe Gly Asn Thr Ala Val 290 295 300 Ala Lys Cys Asn Val Asn His Asp Glu Glu Phe Cys Asp Met Leu Arg 305 310 315 320 Leu Ile Asp Tyr Asn Lys Ala Ala Leu Ser Lys Phe Lys Gln Asp Val 325 330 335 Glu Ser Ala Leu His Val Phe Lys Thr Thr Val Asn Ser Leu Ile Ser 340 345 350 Asp Gln Leu Leu Met Arg Asn His Leu Arg Asp Leu Met Gly Val Pro 355 360 365 Tyr Cys Asn Tyr Ser Lys Phe Trp Tyr Leu Glu His Ala Lys Thr Gly 370 375 380 Glu Thr Ser Val Pro Lys Cys Trp Leu Val Thr Asn Gly Ser Tyr Leu 385 390 395 400 Asn Glu Thr His Phe Ser Asp Gln Ile Glu Gln Glu Ala Asp Asn Met 405 410 415 Ile Thr Glu Met Leu Arg Lys Asp Tyr Ile Lys Arg Gln Gly Ser Thr 420 425 430 Pro Leu Ala Leu Met Asp Leu Leu Met Phe Ser Thr Ser Ala Tyr Leu 435 440 445 Ile Ser Ile Phe Leu His Leu Val Lys Ile Pro Thr His Arg His Ile 450 455 460 Lys Gly Gly Ser Cys Pro Lys Pro His Arg Leu Thr Asn Lys Gly Ile 465 470 475 480 Cys Ser Cys Gly Ala Phe Lys Val Pro Gly Val Lys Thr Ile Trp Lys 485 490 495 Arg Arg <210> 4 <211> 1497 <212> DNA <213> Lymphocytic choriomeningitis virus <220> <221> MISC_FEATURE <223> Lymphocytic choriomeningitis virus mutant p42 glycoprotein; ssRNA Amphisone-stranded virus; Arenaviridae; Arenavirus; Old World Arenavirus <400> 4 atgggtcaga ttgtgacaat gtttgaggct ttgcctcaca tcattgatga ggtcatcaac 60 attgtcatta ttgtgctcat tataatcacg agcatcaaag ctgtgtacaa tttcgccacc 120 tgtgggatat tagcactggt cagcttcctt tttttggctg gtaggtcctg tggcatgtac 180 ggccttaatg gtcccgacat ctataaaggg gtttaccagt tcaaatcagt ggagtttgat 240 atgtctcact taaatctgac gatgcccaat gcgtgctcag ccaacaactc tcatcactac 300 atcagtatgg gaagctctgg actggagcta actttcacta acgactccat ccttaatcac 360 aatttttgca acttaacctc cgctttcaac aaaaagactt ttgaccatac actcatgagt 420 atagtctcga gtctgcacct cagtattaga gggaattcca accacaaagc agtgtcttgt 480 gattttaaca atggcatcac cattcaatac aacttgtcat tttcggaccc acagagcgct 540 atgagccagt gtaggacttt cagaggtaga gtcttggaca tgtttagaac tgcctttgga 600 ggaaaataca tgagaagtgg ctggggctgg gcaggttcag atggcaagac cacttggtgc 660 agccaaacaa gctatcagta cctaatcata caaaacagga cttgggaaaa ccactgtaga 720 tatgcaggcc cttttgggat gtctagaatc ctctttgctc aggaaaagac aaagtttctc 780 actaggagac ttgcaggcac attcacctgg accctgtcag actcctcagg agtagaaaat 840 ccaggtggtt attgcctgac caaatggatg atccttgctg cagagctcaa atgttttggg 900 aatacagctg ttgcaaaatg taatgtcaat catgatgaag agttctgtga catgctacga 960 ctaattgatt acaacaaggc cgccctgagt aagttcaagc aagatgtaga gtctgccttg 1020 catgtattca aaacaacagt aaattcttg atttccgatc agctgttgat gaggaatcat 1080 ctaagagatc taatgggggt accatactgt aattactcaa agttctggta tctggaacat 1140 gctaagactg gtgagactag tgtacccaag tgctggcttg tcactaatg ctcctacttg 1200 aatgagaccc actttagtga tcaaatcgaa caagaagcag ataacatgat cacagagatg 1260 ttgaggaagg actacataaa aagacaaggg agtactcctt tagccttaat ggatctttttg 1320 atgttttcaa catcagcata tctaatcagc atctttctgc atcttgtgaa gataccaaca 1380 catagacaca taaagggcgg ttcatgtcca aagccacaccc gcttgaccaa caaggggatc 1440 tgtagttgtg gtgcattcaa ggtgcctggt gtaaaaacta tctggaaaag acgctga 1497 <210> 5 <211> 2209 <212> PRT <213> Lymphocytic choriomeningitis virus <220> <221> MISC_FEATURE <223> Lymphocytic choriomeningitis virus mutant L-protein; ssRNA Amphisone-stranded virus; Arenaviridae; Arenavirus; Old World Arenavirus <400> 5 Met Asp Glu Thr Ile Ala Asp Leu Arg Glu Leu Cys Leu Asn Tyr Ile 1 5 10 15 Glu Gln Asp Glu Arg Leu Ser Arg Gln Lys Leu Asn Phe Leu Gly Gln 20 25 30 Arg Glu Pro Arg Met Val Leu Ile Glu Gly Leu Lys Leu Leu Ser Arg 35 40 45 Cys Ile Glu Ile Asp Ser Ala Asp Lys Ser Gly Cys Ile His Asn His 50 55 60 Asp Asp Lys Ser Val Glu Thr Ile Leu Ile Asp Ser Gly Ile Val Cys 65 70 75 80 Pro Gly Leu Pro Leu Ile Ile Pro Asp Gly Tyr Lys Leu Ile Asp Asn 85 90 95 Ser Thr Pro Ala Ser Phe 100 105 110 Glu Lys Phe Ile Glu Asp Thr Asn Lys Leu Ala Cys Ile Lys Glu 115 120 125 Asp Leu Ala Val Ala Gly Ile Thr Leu Val Pro Ile Val Asp Gly Arg 130 135 140 Cys Asp Tyr Asp Asn Ser Phe Met Pro Glu Trp Val Asn Phe Lys Phe 145 150 155 160 Arg Asp Leu Phe Lys Leu Glu Tyr Ser Ser Gln Asp Glu Lys 165 170 175 Val Phe Glu Glu Ser Glu Tyr Phe Arg Leu Cys Glu Ser Leu Lys Thr 180 185 190 Thr Val Asp Lys Arg Ser Gly Met Asp Ser Met Lys Ile Leu Lys Asp 195 200 205 Ala Arg Ser Phe His Asn Asp Glu Ile Met Lys Met Cys His Asp Gly 210 215 220 Val Asn Pro Asn Met Ser Cys Asp Asp Val Val Phe Gly Ile Asn Ser 225 230 235 240 Phe Phe Gly Arg Phe Arg Arg Asp Leu Leu Asn Gly Lys Leu Lys Arg 245 250 255 Asn Phe Gln Lys Val Ser Pro Gly Gly Leu Ile Lys Glu Phe Ser Glu 260 265 270 Leu Tyr Glu Thr Leu Thr Asp Asn Asp Asp Ile Leu Met Leu Ser Lys 275 280 285 Glu Ala Val Glu Ser Cys Pro Leu Met Arg Phe Ile Thr Ala Glu Thr 290 295 300 His Gly His Glu Arg Gly Ser Asp Ala Asn Thr Glu Tyr Glu Arg Leu 305 310 315 320 Leu Ser Met Leu Asn Lys Val Lys Ser Leu Lys Leu Leu Asn Thr Arg 325 330 335 Arg Arg Gln Leu Leu Asn Leu Asp Val Leu Cys Leu Ser Ser Leu Ile 340 345 350 Lys Gln Ser Ile Ser Lys Gly Leu Glu Asn Asp Lys His Trp Val Gly 355 360 365 Cys Cys Tyr Ser Ser Val Asn Asp Arg Leu Val Ser Leu Gln Ser Thr 370 375 380 Lys Glu Glu Phe Met Arg Leu Leu Lys Asn Arg Arg Lys Ser Arg Val 385 390 395 400 His Lys Lys Ala Ser Leu Asp Glu Leu Phe Arg Val Ser Ile Asn Glu 405 410 415 Phe Ile Ala Lys Ile Gln Lys Cys Leu Ser Thr Val Gly Leu Ser Phe 420 425 430 Glu His Tyr Gly Leu Ser Glu Cys Leu Val Gln Glu Cys His Ile Pro 435 440 445 Phe Ala Glu Phe Glu Asn Phe Met Arg Ala Gly Thr His Pro Val Met 450 455 460 His Tyr Thr Lys Phe Glu Asp Tyr Thr Phe Gln Pro Asn Ile Glu Gln 465 470 475 480 Leu Arg Gly Leu Gln Ser Leu Arg Lys Leu Ser Ser Val Cys Leu Ala 485 490 495 Leu Thr Asn Ser Met Lys Thr Ser Ser Val Ala Arg Leu Arg Gln Asn 500 505 510 Gln Leu Gly Ser Val Arg Tyr Gln Val Val Glu Cys Lys Glu Val Phe 515 520 525 Cys Gln Ile Ile Lys Leu Asp Ser Glu Glu Tyr His Leu Leu Tyr Gln 530 535 540 Lys Thr Gly Glu Ser Ser Arg Cys Tyr Ser Ile Gln Gly Pro Asp Gly 545 550 555 560 His Leu Ile Ser Phe Tyr Ala Asp Pro Lys Arg Phe Phe Leu Pro Ile 565 570 575 Phe Ser Asp Glu Val Leu His Asn Met Ile Asp Thr Met Ile Ser Trp 580 585 590 Ile Arg Ser Cys Pro Asp Leu Lys Asp Ser Leu Ile Asp Ile Glu Thr 595 600 605 Ala Leu Arg Thr Leu Ile Leu Leu Met Leu Thr Asn Pro Thr Lys Arg 610 615 620 Asn Gln Lys Gln Val Gln Asn Ile Arg Tyr Leu Val Met Ala Ile Val 625 630 635 640 Ser Asp Phe Ser Ser Thr Ser Leu Met Asp Lys Leu Lys Glu Asp Leu 645 650 655 Ile Thr Pro Ala Glu Lys Val Val Tyr Arg Leu Leu Arg Phe Leu Ile 660 665 670 Arg Thr Ile Phe Gly Thr Gly Glu Lys Val Leu Leu Ser Ala Lys Phe 675 680 685 Lys Phe Met Leu Asn Val Ser Tyr Leu Cys His Leu Ile Thr Lys Glu 690 695 700 Thr Pro Asp Arg Leu Thr Asp Gln Ile Lys Cys Phe Glu Lys Phe Phe 705 710 715 720 Glu Pro Lys Ser Glu Phe Gly Phe Phe Val Asn Pro Lys Glu Thr Ile 725 730 735 Thr Pro Glu Glu Glu Cys Val Phe Tyr Glu Gln Met Lys Lys Phe Thr 740 745 750 Gly Lys Asp Ile Asp Cys Gln His Ser Thr Pro Gly Val Asn Leu Glu 755 760 765 Ile Phe Ser Met Met Val Ser Ser Phe Asn Asn Gly Thr Leu Ile Leu 770 775 780 Lys Gly Glu Lys Arg Leu Asn Asn Leu Asp Pro Met Thr Asn Ser Gly 785 790 795 800 Cys Ala Thr Ala Leu Asp Leu Ala Ser Asn Lys Ser Val Val Val Asn 805 810 815 Lys His Leu Asn Gly Glu Arg Leu Leu Glu Tyr Asp Phe Asn Lys Leu 820 825 830 Leu Val Ser Ala Val Ser Gln Ile Thr Glu Gly Phe Met Arg Lys Gln 835 840 845 Lys Tyr Lys Leu Arg His Ser Asp Tyr Glu Tyr Lys Val Ser Lys Leu 850 855 860 Val Ser Arg Leu Val Ile Gly Ser Arg Lys Thr Glu Val Asp Lys Leu 865 870 875 880 Glu Asp Asp Pro Val Asp Val Cys Phe Glu Gly Glu Glu Glu Thr Ser 885 890 895 Phe Phe Arg Ser Leu Glu Asp Lys Val Ser Ser Thr Ile Thr Arg Tyr 900 905 910 Asn Arg Gly Thr Arg Leu Asn Glu Gly Gln Gly Glu Gly Glu Phe Lys 915 920 925 Asn Thr Lys Gly Leu His His Leu Gln Ile Ile Leu Ser Gly Lys Arg 930 935 940 Ala Tyr Leu Arg Lys Val Ile Leu Ser Glu Ile Ser Phe His Leu Val 945 950 955 960 Glu Asp Phe Asp Pro Ser Cys Leu Thr Asn Asp Asp Met Arg Phe Ile 965 970 975 Cys Glu Ala Val Glu Gly Ser Thr Glu Leu Ser Pro Leu Tyr Phe Thr 980 985 990 Ser Ala Val Lys Glu Gln Cys Gly Leu Asp Glu Met Ala Arg Asn Leu 995 1000 1005 Cys Arg Lys Phe Phe Ser Glu Gly Asp Trp Phe Ser Cys Met Lys 1010 1015 1020 Met Ile Leu Leu Gln Met Asn Ala Asn Ala Tyr Ser Gly Lys Tyr 1025 1030 1035 Arg His Met Gln Arg Gln Ser Leu Asn Phe Lys Phe Asp Trp Asp 1040 1045 1050 Lys Leu Glu Glu Asp Val Arg Ile Ser Glu Arg Glu Ser Asn Ser 1055 1060 1065 Glu Ser Leu Ser Lys Ala Leu Ser Leu Thr Lys Cys Met Ser Ala 1070 1075 1080 Ala Leu Lys Asn Leu Cys Phe Tyr Ser Glu Glu Ser Pro Thr Ser 1085 1090 1095 Tyr Thr Ser Val Gly Pro Asp Ser Gly Arg Leu Lys Phe Ala Leu 1100 1105 1110 Ser Tyr Lys Glu Gln Val Gly Gly Asn Arg Glu Leu Tyr Ile Gly 1115 1120 1125 Asp Leu Arg Thr Lys Met Phe Thr Arg Leu Val Glu Asp Tyr Phe 1130 1135 1140 Glu Ser Phe Ser Ser Phe Phe Ser Gly Ser Cys Leu Asn Asn Asp 1145 1150 1155 Lys Glu Phe Glu Asn Ala Ile Leu Ser Met Thr Ile Asn Val Arg 1160 1165 1170 Glu Gly Leu Leu Asn Tyr Ser Met Asp His Ser Lys Trp Gly Pro 1175 1180 1185 Met Met Cys Pro Phe Leu Phe Leu Met Leu Leu Gln Asn Leu Lys 1190 1195 1200 Leu Gly Asp Asp Gln Tyr Val Arg Ser Gly Lys Asp His Val Ser 1205 1210 1215 Thr Leu Leu Thr Trp His Met His Lys Leu Val Glu Val Pro Phe 1220 1225 1230 Pro Val Val Asn Ala Met Met Lys Ser Tyr Val Lys Ser Lys Leu 1235 1240 1245 Lys Leu Leu Lys Gly Ser Gly Thr Thr Val Thr Glu Arg Ile Phe 1250 1255 1260 Arg Glu Tyr Phe Glu Met Gly Val Val Pro Ser His Ile Ser Ser 1265 1270 1275 Leu Ile Asp Met Gly Gln Gly Ile Leu His Asn Ala Ser Asp Phe 1280 1285 1290 Tyr Gly Leu Ile Ser Glu Arg Phe Ile Asn Tyr Cys Ile Gly Val 1295 1300 1305 Ile Phe Gly Glu Arg Pro Glu Ala Tyr Thr Ser Ser Asp Asp Gln 1310 1315 1320 Ile Thr Leu Phe Asp Lys Arg Leu Ser Asp Leu Val Asp Ser Asp 1325 1330 1335 Pro Glu Glu Val Leu Val Leu Leu Glu Phe His Ser His Leu Ser 1340 1345 1350 Gly Leu Leu Asn Lys Phe Ile Ser Pro Lys Ser Val Val Gly Arg 1355 1360 1365 Phe Ala Ala Glu Phe Lys Ser Arg Phe Tyr Val Trp Gly Glu Glu 1370 1375 1380 Val Pro Leu Leu Thr Lys Phe Val Ser Ala Ala Leu His Asn Val 1385 1390 1395 Lys Cys Lys Glu Pro His Gln Leu Cys Glu Thr Ile Asp Thr Ile 1400 1405 1410 Ala Asp Gln Ala Ile Ala Asn Gly Val Pro Val Phe Leu Val Asn 1415 1420 1425 Cys Ile Gln Arg Arg Thr Leu Asp Leu Leu Lys Tyr Ala Asn Phe 1430 1435 1440 Pro Leu Asp Pro Phe Leu Leu Asn Thr His Thr Asp Val Lys Asp 1445 1450 1455 Trp Leu Asp Gly Ser Arg Gly Tyr Arg Ile Gln Arg Leu Ile Glu 1460 1465 1470 Glu Leu Cys Pro Ser Glu Thr Lys Ile Met Arg Lys Leu Val Arg 1475 1480 1485 Arg Leu His His Lys Leu Lys Asn Gly Glu Cys Asn Glu Glu Phe 1490 1495 1500 Phe Leu Asp Leu Phe Asn Arg Glu Lys Glu Glu Ala Ile Leu Gln 1505 1510 1515 Leu Gly Glu Ile Leu Gly Leu Glu Asp Asp Leu Asn Glu Leu Ala 1520 1525 1530 Ser Ile Asn Trp Leu Asn Leu Asn Glu Met Phe Pro Leu Arg Met 1535 1540 1545 Val Leu Arg Gln Lys Val Val Tyr Pro Ser Val Met Thr Phe Gln 1550 1555 1560 Glu Glu Lys Ile Pro Ser Leu Ile Lys Thr Leu Gln Asn Lys Leu 1565 1570 1575 Cys Ser Lys Phe Thr Arg Gly Ala Gln Lys Leu Leu Ser Glu Ala 1580 1585 1590 Ile Asn Lys Ser Ala Phe Gln Ser Cys Val Ser Ser Gly Phe Ile 1595 1600 1605 Gly Leu Cys Lys Thr Leu Gly Ser Arg Cys Val Arg Asn Lys Asn 1610 1615 1620 Arg Glu Asn Met Tyr Ile Arg Lys Val Leu Glu Asp Leu Thr Met 1625 1630 1635 Asp Glu His Val Thr Arg Val His Lys Gln Asp Gly Val Met Leu 1640 1645 1650 Tyr Ile Cys Asp Lys Gln Arg His Pro Glu Ala His Arg Asp His 1655 1660 1665 Ile Asn Leu Leu Arg Pro Leu Leu Trp Asp Tyr Ile Cys Ile Ser 1670 1675 1680 Leu Ser Asn Ser Phe Glu Leu Gly Val Trp Val Leu Ala Glu Pro 1685 1690 1695 Val Lys Gly Lys Asn Glu Ser Asn Ser Ala Val Arg His Leu Asn 1700 1705 1710 Pro Cys Asp Tyr Val Ala Arg Lys Pro Glu Ser Ser Arg Leu Leu 1715 1720 1725 Glu Asp Lys Val Ser Leu Asn His Val Ile Gln Ser Val Arg Arg 1730 1735 1740 Leu Tyr Pro Lys Ile Phe Glu Asp Gln Leu Leu Pro Phe Met Ser 1745 1750 1755 Asp Val Ser Ser Lys Asn Met Arg Trp Ser Pro Arg Ile Lys Phe 1760 1765 1770 Leu Asp Leu Cys Val Leu Ile Asp Ile Asn Ser Glu Ser Leu Ser 1775 1780 1785 Leu Ile Ser His Val Val Lys Trp Lys Arg Asp Glu His Tyr Thr 1790 1795 1800 Val Leu Phe Ser Asp Leu Val Asn Ser His Gln Arg Ser Asp Ser 1805 1810 1815 Ser Leu Val Asp Glu Phe Val Val Ser Thr Arg Asp Val Cys Lys 1820 1825 1830 Asn Phe Leu Lys Gln Val Tyr Phe Glu Ser Phe Val Arg Glu Phe 1835 1840 1845 Val Ala Thr Ala Arg Thr Leu Gly Asn Phe Ser Trp Phe Pro His 1850 1855 1860 Lys Asp Met Met Pro Ser Glu Asp Gly Ala Glu Ala Leu Gly Pro 1865 1870 1875 Phe Gln Ser Phe Ile Leu Lys Val Val Asn Lys Lys Ile Glu Arg 1880 1885 1890 Pro Met Phe Arg Asn Asp Leu Gln Phe Gly Phe Gly Trp Phe Ser 1895 1900 1905 Tyr Arg Val Gly Asp Val Val Cys Asn Ala Ala Met Leu Ile Lys 1910 1915 1920 Gln Gly Leu Thr Asp Pro Lys Ala Phe Lys Ser Leu Arg Asp Leu 1925 1930 1935 Trp Asp Tyr Met Leu Ser Ser Thr Glu Gly Ile Leu Glu Phe Ser 1940 1945 1950 Ile Thr Val Asp Phe Thr His Asn Gln Asn Asn Thr Asp Cys Leu 1955 1960 1965 Arg Lys Phe Ser Leu Ile Phe Val Val Lys Cys Gln Leu Gln Ser 1970 1975 1980 Pro Gly Val Ala Asp Tyr Leu Ser Cys Ser His Ser Phe Lys Gly 1985 1990 1995 Glu Val Asp Arg Arg Leu Leu Asp Glu Cys Leu Asn Leu Leu Arg 2000 2005 2010 Thr Asp Pro Ile Phe Lys Ala Asn Asp Gly Val Phe Asp Ile Arg 2015 2020 2025 Ser Glu Glu Phe Glu Asp Tyr Met Glu Asp Pro Leu Thr Leu Gly 2030 2035 2040 Asp Ser Leu Glu Leu Glu Leu Ile Gly Ser Arg Arg Ile Leu Asn 2045 2050 2055 Glu Ile Lys Ser Thr Asp Phe Glu Arg Ile Gly Pro Glu Trp Glu 2060 2065 2070 Pro Val Pro Leu Thr Ile Arg Lys Gly Ala Leu Phe Glu Gly Arg 2075 2080 2085 Asn Phe Val Gln Asn Ile Ser Val Lys Leu Glu Thr Lys Asp Met 2090 2095 2100 Arg Val Phe Leu Ala Glu Leu Glu Gly Cys Gly Lys Ile Gly Asp 2105 2110 2115 Val Leu Gly Ser Leu Leu Leu His Arg Phe Arg Thr Gly Glu His 2120 2125 2130 Leu Met Glu Ser Glu Ile Ser Thr Val Leu Gln Glu Leu Cys Met 2135 2140 2145 Asp Arg Ser Val Met Leu Thr Pro Leu Ser Phe Val Pro Asp Trp 2150 2155 2160 Phe Thr Phe Arg Asp Cys Arg Leu Cys Phe Ser Lys Ser Lys Asn 2165 2170 2175 Thr Val Met Tyr Glu Thr Thr Gly Gly Arg Phe Arg Leu Lys Gly 2180 2185 2190 Lys Ser Cys Asp Asp Trp Leu Ala Glu Arg Val Ala Glu Glu Ile 2195 2200 2205 Asp <210> 6 <211> 6630 <212> DNA <213> Lymphocytic choriomeningitis virus <220> <221> MISC_FEATURE <223> Lymphocytic choriomeningitis virus mutant L-protein; ssRNA Amphisone-stranded virus; Arenaviridae; Arenavirus; Old World Arenavirus <400> 6 atggatgaaa ctattgcaga tttgagagag ttgtgtctaa attacataga acaggacgag 60 aggctgtcaa ggcaaaaact caacttcctg ggacaaagag aacccagaat ggtgctaatt 120 gagggactca aattgttatc acgctgtata gagatagaca gtgcagacaa aagtggttgc 180 atacacaacc acgatgacaa atctgttgaa acaatcctaa tagactctgg gattgtgtgt 240 ccaggactgc cactcatcat ccctgatggt tataagttga ttgacaattc ccttattctt 300 cttgaatgtt ttgttagaag cacaccagct agttttgaaa agaagttcat tgaggacacc 360 aacaaactag catgcatcaa agaagatctt gctgttgcag gcatcacact ggttccaata 420 gtggatggtc gttgtgatta tgataacagt ttcatgccag aatgggtgaa ttttaagttc 480 agagacctcc tatttaaact cctggagtat tctagtcaag atgagaaagt ttttgaggag 540 tctgaatact tcaggctctg tgagtctctt aagaccactg ttgacaaacg ttccggcatg 600 gactcaatga aaattttgaa agacgcaaga tcatttcata acgatgagat tatgaaaatg 660 tgccacgatg gtgtcaaccc caacatgagt tgcgatgatg tggtctttgg cataaattcc 720 tttttggca ggtttaggag ggacctgtta aatgggaaac tcaaaaggaa tttccaaaag 780 gtcagccctg ggggcttaat caaggaattc tctgaacttt atgaaaccct tactgataat 840 gatgacatat taatgttgag caaagaggca gttgaatcct gccccttaat gaggttcatt 900 960 ctctctatgt tgaacaaggt gaaaagttta aaattattaa acactagaag gagacagctg 1020 ctgaacttag atgtcttatg tctttcttca cttattaagc agtcaatttc caaagggttg 1080 gaaaatgata aacattgggt tggttgctgc tacagtagtg tgaatgatag gcttgtgagc 1140 cttcaaagta ccaaagaaga attcatgaga cttttgaaga acagaagaaa atcaagagtg 1200 cacaaaaagg catctcttga tgagcttttt agggtatcca taaatgagtt catagcaaaa 1260 atccagaaat gcctatcaac agtgggactt agttttgagc attacggact atcagaatgc 1320 ctcgtgcaag aatgccatat accatttgct gaatttgaga actttatgag agccgggact 1380 catcctgtaa tgcattacac aaaatttgaa gattacactt tccagcctaa catagagcaa 1440 ttgaggggtt tacagagttt gagaaaactg tcatctgttt gtttggctct aacaaacagc 1500 atgaaaacaa gctcagttgc aaggttgaga cagaaccaac tggggtctgt gagatatcaa 1560 gtggtggagt gcaaagaggt gttttgccag ataataaaac tggattccga agagtatcat 1620 ctactatatc agaaaactgg agaatcatcg aggtgttatt ccatacaagg tccggatggt 1680 cacttgattt ccttttacgc agatccaaaa aggttctttt taccaattttt ttcagatgag 1740 gtgttgcaca acatgataga cacaatgatt tcatggatta ggtcatgccc tgacttaaaa 1800 gattctctta ttgacattga gactgcacta aggacattga tcctactgat gctcaccaac 1860 ccaacaaaga gaaatcaaaa gcaggttcaa aatattaggt atttagtgat ggccatcgtc 1920 tcagacttt catcgacctc attaatggat aagttgaagg aggatctaat cacacctgcc 1980 gagaaagtgg tgtacaggct gcttcggtttt ttgattagga caatttttgg tactggtgaa 2040 aaggtgttat tgagtgcaaa attcaagttt atgttgaatg tgtcatacct gtgtcatttg 2100 atcacaaagg agacccctga tagattgaca gatcagataa aatgttttga aaagttcttt 2160 gagcccaaga gtgagtttgg tttctttgtc aaccctaagg aaacaatcac acccgaagag 2220 gaatgtgttt tttatgaaca aatgaagaag ttcaccggta aagatattga ttgtcagcat 2280 tcaacccctg gtgttaattt agagatcttt agcatgatgg tatcttcatt caacaatggc 2340 accttaattc taaaagggga gaaaaggctc aacaatctgg accccacatgac caactctgga 2400 tgtgcgacag cattagatct cgcaagcaac aaaagtgtgg ttgtcaataa acatctgaat 2460 ggagaacggc ttttggagta tgattttaac aaattgcttg ttagtgctgt gagccaaatt 2520 acagagggct tcatgaggaa acaaaagtat aagctgagac actcagatta cgaatataag 2580 gtctcaaagc ttgtctctag attagtcatc ggttccagga aaacagaagt agacaaattg 2640 gaagatgatc cggtagatgt gtgtttcgag ggggaggagg agacaagttt tttcaggagt 2700 ttagaagata aggtcagctc cacaataaca cggtataata gaggcactag gcttaatgaa 2760 gggcaagggg agggagaatt caagaacaca aaaggactac accaccttca gattattttg 2820 tcaggtaaaa gagcttatct gaggaaagtc attttatcag aaatttcatt tcatctagta 2880 gaggactttg atccatcctg tctcaccaat gacgacatga ggtttatttg tgaggctgtt 2940 gaaggttcaa cagaactgtc accattgtat tttacatcag ctgtcaaaga acaatgtggt 3000 ctggatgaga tggcaagaaa cctctgtaga aagttcttct cagagggtga ttggttctca 3060 tgtatgaaga tgatcttgtt acagatgaat gcaaatgcgt attcagggaa gtacagacac 3120 atgcagaggc agagcttaaa ttttaaattt gactgggaca aattggaaga agatgtaaga 3180 attagtgaaa gggaaagcaa ttctgaatct ctaagtaagg ccctttcatt gacaaaatgc 3240 atgagtgctg ctctaaagaa tctgtgtttt tactcagaag aatcaccaac atcatacact 3300 tcagttggcc ctgactctgg gagactaaaa tttgcattgt catacaaaga gcaggttggg 3360 ggaatagag agctttacat tggggatttg aggacaaaaa tgttcacaag attggtagaa 3420 gattattttg aatccttttc tagtttctt tcaggatctt gttaaacaa tgataaagag 3480 tttgaaaatg caatcttgtc aatgactatc aatgtgagag aagggttgtt aaactacagc 3540 atggatcaca gcaaatgggg accaatgatg tgcccattcc tattcttaat gcttctccaa 3600 aatctcaaac tgggtgatga tcagtacgtg cgttctggaa aagatcatgt tagcaccttg 3660 ttgacttggc atatgcataa acttgttgaa gtccctttcc ctgttgtgaa tgcaatgatg 3720 aaatcatatg ttaaatcaaa actcaagctt ctcaaagggt caggaacgac tgttacggag 3780 agaatcttta gagagtattt tgaaatgggg gtggtgccat ctcacatatc tagtctcatt 3840 gacatgggac aggggatcct acacaatgct tctgattttt acggtttaat tagtgaaagg 3900 tttatcaatt attgtattgg tgtcattttt ggagagaggc cagaagccta tacatcaagt 3960 gatgatcaga tcactttatt tgacaagaga ttgagtgact tagttgatag tgacccagaa 4020 gaagtccttg tcttgctgga attccactct cacttaagtg gtttgttgaa caagttcatc 4080 agtccaaaaa gtgtggttgg gcggtttgca gcggaattca aatccagatt ttatgtgtgg 4140 ggggaggagg tccctctcct cacgaaattt gtgtctgcgg cactacacaa tgttaagtgt 4200 aaagaaccgc atcaactttg tgagacaata gatacgattg ctgatcaagc tatagcaaat 4260 ggagttccag tttttgt aactgtatc cagaggagga cactggatct cttgaaatat 4320 gctaatttcc ctttagatcc attcttgtta aacactcaca ctgatgtaaa ggattggtta 4380 gatggttcta gaggttatag atccaaga ctcattgaag aattgtgtcc cagtgaaaca 4440 aagatcatga gaaacttgt aagaacta catcacaac tcagaacgg tgaatgtaac 4500 gaggaatttt ttcagacct cttcacagg gaaaggaag aggcatcct tcattggga 4560 gagattcttg gtcttgagga tgatcttaat gagttggcaa gcatcattg gttgaatctg 4620 aatgaaatgt tcccattgag gatggttctg agacaaaag tggtttaccc atcagtaatg 4680 accttcaag aggaaagat cccctcattg attaaaacc tccaaaataa gctttgtagt 4740 aagttcaca gaggtgcaca gaagctgttg tcagaggcaa tcaaatc agcttttcag 4800 agttgtgtct catccggctt tataggtctc tgtaagactt taggagtag gtgtgtgaga 4860 aaaaaaaca gggaaaatat gtatatcaga aaggtgcttg aagatctgac catggatgaa 4920 catgtcaca gggttcacaa acatttgt gtgatgttgt acatttgcga caacagaga 4980 cacccagagg ctcaccgtga ccacatcaac cttttgaggc cccttctctg ggactacatt 5040 tgcatctcat tgagcaactc ttttgagctg ggtgtttggg ttttagcaga acctgtgaaa 5100 ggaaagaacg agagtaattc ggctgttagg cacttaaatc catgtgatta tgtagcaaga 5160 aaacctgaga gttcgagact actagaggat aaagtgagtt tgaatcatgt aattcaatct 5220 gtgaggcgac tgtaccccaa aatctttgag gatcagttgc tcccattcat gtctgatgtg 5280 agctcaaaaa atatgagatg gagtcccagg attaaattcc ttgacctttg tgtgctgatt 5340 gacatcaact cagagtcttt gtcactcatt tctcatgttg tcaaatggaa gagggacgaa 5400 cattacactg tgctgttttc tgatctcgtc aactctcacc aacggtcaga ctcaagttta 5460 gttgatgaat ttgttgtcag cacaagggat gtctgcaaga actttttgaa gcaagtgtat 5520 ttcgaatcat ttgtacgaga gtttgttgca acagctagga ccttaggtaa cttttcatgg 5580 ttcccccata aggacatgat gccatctgaa gatggcgctg aagcactggg acccttccaa 5640 tcatttattt tgaaagtggt gaacaagaaa atagagaggc ccatgtttag gaatgacttg 5700 cagtttggtt ttggttggtt ccttatcgt gtgggggatg ttgtgtgtaa tgccgctatg 5760 ttaattaagc agggtttgac agatccaaaa gcatttaaat ctttaagaga tttgtgggat 5820 tacatgctca gcagcacaga ggggatattg gagttctcaa tcacagtgga tttcacacac 5880 aaccagaaca acactgactg cttgaggaaa ttttcattga tctttgtggt taaatgccaa 5940 ttacagagtc caggtgtagc tgattactta tcgtgctctc attccttcaa aggtgaggtt 6000 gacaggagat tattagatga gtgtctcaat ctgttgagga cagaccccat cttaaagcg 6060 aatgatggag tctttgacat taggtctgaa gagtttgaag attacatgga agaccctttg 6120 acacttggtg attcactaga acttgaacta ataggttcta gaaggattct gaatgagatc 6180 aaatctactg actttgagag gatagggcct gagtgggaac ctgtgcctct gaccataagg 6240 aagggtgccc tctttgaggg gaggaacttt gttcagaata tctctgtgaa attggagaca 6300 aaggacatga gggtctttct ggcagagctc gagggctgtg gaaaaattgg tgatgtcctc 6360 ggcagcctcc tcctgcaccg attcagaact ggtgagcact tgatggagtc agaaataagt 6420 acagttcttc aggagctctg catggacaga tccgtcatgc tgacaccatt atcttttgtg 6480 ccagattggt tcaccttcag agattgtagg ctctgcttca gcaagtcaaa gaacactgta 6540 atgtatgaga caactggggg caggttcaga ctcaagggga aatcctgtga cgattggctg 6600 gcggagcggg tggccgagga gatcgactag 6630 <210> 7 <211> 2209 <212> PRT <213> Lymphocytic choriomeningitis virus <220> <221> MISC_FEATURE <223> Lymphocytic choriomeningitis virus wild-type L-protein; ssRNA Amphisone-stranded virus; Arenaviridae; Arenavirus; Old World Arenavirus <400> 7 Met Asp Glu Thr Ile Ala Asp Leu Arg Glu Leu Cys Leu Asn Tyr Ile 1 5 10 15 Glu Gln Asp Glu Arg Leu Ser Arg Gln Lys Leu Asn Phe Leu Gly Gln 20 25 30 Arg Glu Pro Arg Met Val Leu Ile Glu Gly Leu Lys Leu Leu Ser Arg 35 40 45 Cys Ile Glu Ile Asp Ser Ala Asp Lys Ser Gly Cys Ile His Asn His 50 55 60 Asp Asp Lys Ser Val Glu Thr Ile Leu Ile Asp Ser Gly Ile Val Cys 65 70 75 80 Pro Gly Leu Pro Leu Ile Ile Pro Asp Gly Tyr Lys Leu Ile Asp Asn 85 90 95 Ser Leu Ile Leu Leu Glu Cys Phe Val Arg Ser Thr Pro Ala Ser Phe 100 105 110 Glu Lys Lys Phe Ile Glu Asp Thr Asn Lys Leu Ala Cys Ile Lys Glu 115 120 125 Asp Leu Ala Val Ala Gly Ile Thr Leu Val Pro Ile Val Asp Gly Arg 130 135 140 Cys Asp Tyr Asp Asn Ser Phe Met Pro Glu Trp Val Asn Phe Lys Phe 145 150 155 160 Arg Asp Leu Leu Phe Lys Leu Leu Glu Tyr Ser Ser Gln Asp Glu Lys 165 170 175 Val Phe Glu Glu Ser Glu Tyr Phe Arg Leu Cys Glu Ser Leu Lys Thr 180 185 190 Thr Val Asp Lys Arg Ser Gly Met Asp Ser Met Lys Ile Leu Lys Asp 195 200 205 Ala Arg Ser Phe His Asn Asp Glu Ile Met Lys Met Cys His Asp Gly 210 215 220 Val Asn Pro Asn Met Ser Cys Asp Asp Val Val Phe Gly Ile Asn Ser 225 230 235 240 Phe Phe Gly Arg Phe Arg Arg Asp Leu Leu Asn Gly Lys Leu Lys Arg 245 250 255 Asn Phe Gln Lys Val Ser Pro Gly Gly Leu Ile Lys Glu Phe Ser Glu 260 265 270 Leu Tyr Glu Thr Leu Thr Asp Asn Asp Asp Ile Leu Met Leu Ser Lys 275 280 285 Glu Ala Val Glu Ser Cys Pro Leu Met Arg Phe Ile Thr Ala Glu Thr 290 295 300 His Gly His Glu Arg Gly Ser Asp Ala Asn Thr Glu Tyr Glu Arg Leu 305 310 315 320 Leu Ser Met Leu Asn Lys Val Lys Ser Leu Lys Leu Leu Asn Thr Arg 325 330 335 Arg Arg Gln Leu Leu Asn Leu Asp Val Leu Cys Leu Ser Ser Leu Ile 340 345 350 Lys Gln Ser Ile Ser Lys Gly Leu Glu Asn Asp Lys His Trp Val Gly 355 360 365 Cys Cys Tyr Ser Ser Val Asn Asp Arg Leu Val Ser Leu Gln Ser Thr 370 375 380 Lys Glu Glu Phe Met Arg Leu Leu Lys Asn Arg Arg Lys Ser Arg Val 385 390 395 400 His Lys Lys Ala Served Asp Glu To Phe Arg Val Served Ile Asn Glu 405 410 415 Phe and Ala Lys and Gln Lys Cys can be found in Thr Val Gly 420 425 430 Glu His Tyr Gly Leu Ser Glu Cys Leu Val Gln Glu Cys His Ile Pro 435 440 445 Phe Ala Glu Phe Glu Asn Phe Met Arg Ala Gly Thr His Pro Val Met 450 455 460 His Tyr Thr Lys Phe Glu Asp Tyr Thr Phe Gln Pro Asn Ile Glu Gln 465 470 475 480 Leu Arg Gly Leu Gln Ser Leu Arg Leu Ser Val Cys Leu Wing 485,490,495 Leu Thr Asn Will Be Met Lys Thr Will Be Val Ala Arg Leu Arg Gln Asn 500 505 510 Gln Leu Gly Ser Val Arg Tyr Gln Val Val Glu Cys Lys Glu Val Phe 515,520,525 Cys Gln Ile Ile Lys Leu Asp Ser Glu Glu Tyr His Leu Tyr Gln 530 535 540 Lys Thr Gly Glu Ser Ser Arg Cys Tyr Ser Ile Gln Gly Pro Asp Gly 545 550 555 560 His Leu Ile Ser Phe Tyr Ala Asp Pro Lys Arg Phe Phe Leu Pro Ile 565 570 575 Phe Ser Asp Glu Val Leu His Asn Met Ile Asp Thr Met Ile Ser Trp 580 585 590 Ile Arg Ser Cys Pro Asp Leu Lys Asp Ser Leu Ile Asp Ile Glu Thr 595 600 605 Ala Leu Arg Thr Leu Ile Leu Leu Met Leu Thr Asn Pro Thr Lys Arg 610 615 620 Asn Gln Lys Gln Val Gln Asn Ile Arg Tyr Leu Val Met Ala Ile Val 625 630 635 640 Ser Asp Phe Ser Ser Thr Ser Leu Met Asp Lys Leu Lys Glu Asp Leu 645 650 655 Ile Thr Pro Ala Glu Lys Val Val Tyr Arg Leu Leu Arg Phe Leu Ile 660 665 670 Arg Thr Ile Phe Gly Thr Gly Glu Lys Val Leu Leu Ser Ala Lys Phe 675 680 685 Lys Phe Met Leu Asn Val Ser Tyr Leu Cys His Leu Ile Thr Lys Glu 690 695 700 Thr Pro Asp Arg Leu Thr Asp Gln Ile Lys Cys Phe Glu Lys Phe Phe 705 710 715 720 Glu Pro Lys Ser Glu Phe Gly Phe Phe Val Asn Pro Lys Glu Thr Ile 725 730 735 Thr Pro Glu Glu Glu Cys Val Phe Tyr Glu Gln Met Lys Lys Phe Thr 740 745 750 Gly Lys Asp Ile Asp Cys Gln His Ser Thr Pro Gly Val Asn Leu Glu 755 760 765 Ile Phe Ser Met Met Val Ser Ser Phe Asn Asn Gly Thr Leu Ile Leu 770 775 780 Lys Gly Glu Lys Arg Leu Asn Asn Leu Asp Pro Met Thr Asn Ser Gly 785 790 795 800 Cys Ala Thr Ala Leu Asp Leu Ala Ser Asn Lys Ser Val Val Val Asn 805 810 815 Lys His Leu Asn Gly Glu Arg Leu Leu Glu Tyr Asp Phe Asn Lys Leu 820 825 830 Leu Val Ser Ala Val Ser Gln Ile Thr Glu Gly Phe Met Arg Lys Gln 835 840 845 Lys Tyr Lys Leu Arg His Ser Asp Tyr Glu Tyr Lys Val Ser Lys Leu 850 855 860 Val Ser Arg Leu Val Ile Gly Ser Arg Lys Thr Glu Val Asp Lys Leu 865 870 875 880 Glu Asp Asp Pro Val Asp Val Cys Phe Glu Gly Glu Glu Glu Thr Ser 885 890 895 Phe Phe Arg Ser Leu Glu Asp Lys Val Ser Ser Thr Ile Thr Arg Tyr 900 905 910 Asn Arg Gly Thr Arg Leu Asn Glu Gly Gln Gly Glu Gly Glu Phe Lys 915 920 925 Asn Thr Lys Gly Leu His His Leu Gln Ile Ile Leu Ser Gly Lys Arg 930 935 940 Ala Tyr Leu Arg Lys Val Ile Leu Ser Glu Ile Ser Phe His Leu Val 945 950 955 960 Glu Asp Phe Asp Pro Ser Cys Leu Thr Asn Asp Asp Met Arg Phe Ile 965 970 975 Cys Glu Ala Val Glu Gly Ser Thr Glu Leu Ser Pro Leu Tyr Phe Thr 980 985 990 Ser Ala Val Lys Glu Gln Cys Gly Leu Asp Glu Met Ala Arg Asn Leu 995 1000 1005 Cys Arg Lys Phe Phe Ser Glu Gly Asp Trp Phe Ser Cys Met Lys 1010 1015 1020 Met Ile Leu Gln With Asn Only Asn Only Tyr Ser Gly Lys Tyr 1025 1030 1035 Arg His Met Gln Arg Gln Ser Leu Asn Phe Lys Phe Asp Trp Asp 1040 1045 1050 Lys Leu Glu Glu Asp Val Arg Ile Ser Glu Arg Glu Ser Asn Ser 1055 1060 1065 Glu Ser Leu Ser Lys Ala Leu Ser Thr Lys Cys Met Ser Ala 1070 1075 1080 Ala Leu Lys Asn Leu Cys Phe Tyr Ser Glu Glu Ser Pro Thr Ser 1085 1090 1095 Tyr Thr Ser Val Gly Pro Asp Ser Gly Arg Leu Lys Phe Ala Leu 1100 1105 1110 Tyr Lys Gln Val Gly Gly Asn Arg Glu Leu Tyr Ile Gly 1115 1120 1125 Asp Leu Arg Thr Lys Met Phe Thr Arg Leu Val Glu Asp Tyr Phe 1130 1135 1140 Glu Ser PhE Ser PHE PHE Ser Gly Ser Cys Leu Asn Asn Asp 1145 1150 1155 Lys Glu Phe Glu Asn Ala Ile Leu Ser Met Thr Ile Asn Val Arg 1160 1165 1170 Glu Gly Leu Leu Asn Tyr Ser Met Asp His Ser Lys Trp Gly Pro 1175 1180 1185 Met Met Cys Pro Phe Leu Phe Leu Met Leu Leu Gln Asn Leu Lys 1190 1195 1200 Leu Gly Asp Asp Gln Tyr Val Arg Ser Gly Lys Asp His Val Ser 1205 1210 1215 Thr Leu Leu Thr Trp His Met His Lys Leu Val Glu Val Pro Phe 1220 1225 1230 Pro Val Val Asn Ala Met Met Lys Ser Tyr Val Lys Ser Lys Leu 1235 1240 1245 Lys Leu Leu Lys Gly Ser Gly Thr Thr Val Thr Glu Arg Ile Phe 1250 1255 1260 Arg Glu Tyr Phe Glu Met Gly Val Val Pro Ser His Ile Ser Ser 1265 1270 1275 Leu Ile Asp Met Gly Gln Gly Ile Leu His Asn Ala Ser Asp Phe 1280 1285 1290 Tyr Gly Leu Ile Ser Glu Arg Phe Ile Asn Tyr Cys Ile Gly Val 1295 1300 1305 Ile Phe Gly Glu Arg Pro Glu Ala Tyr Thr Ser Ser Asp Asp Gln 1310 1315 1320 Ile Thr Leu Phe Asp Lys Arg Leu Ser Asp Leu Val Asp Ser Asp 1325 1330 1335 Pro Glu Glu Val Leu Val Leu Leu Glu Phe His Ser His Leu Ser 1340 1345 1350 Gly Leu Leu Asn Lys Phe Ile Ser Pro Lys Ser Val Val Gly Arg 1355 1360 1365 Phe Ala Ala Glu Phe Lys Ser Arg Phe Tyr Val Trp Gly Glu Glu 1370 1375 1380 Val Pro Leu Leu Thr Lys Phe Val Ser Ala Ala Leu His Asn Val 1385 1390 1395 Lys Cys Lys Glu Pro His Gln Leu Cys Glu Thr Ile Asp Thr Ile 1400 1405 1410 Ala Asp Gln Ala Ile Ala Asn Gly Val Pro Val Phe Leu Val Asn 1415 1420 1425 Cys Ile Gln Arg Arg Thr Leu Asp Leu Leu Lys Tyr Ala Asn Phe 1430 1435 1440 Pro Leu Asp Pro Phe Leu Leu Asn Thr His Thr Asp Val Lys Asp 1445 1450 1455 Trp Leu Asp Gly Ser Arg Gly Tyr Arg Ile Gln Arg Leu Ile Glu 1460 1465 1470 Glu Leu Cys Pro Ser Glu Thr Lys Ile Met Arg Lys Leu Val Arg 1475 1480 1485 Arg Leu His His Lys Leu Lys Asn Gly Glu Cys Asn Glu Glu Phe 1490 1495 1500 Phe Leu Asp Leu Phe Asn Arg Glu Lys Lys Glu Ala Ile Leu Gln 1505 1510 1515 Leu Gly Glu Ile Leu Gly Leu Glu Asp Asp Leu Asn Glu Leu Ala 1520 1525 1530 Ser Ile Asn Trp Leu Asn Leu Asn Glu Met Phe Pro Leu Arg Met 1535 1540 1545 Val Leu Arg Gln Lys Val Val Tyr Pro Ser Val Met Thr Phe Gln 1550 1555 1560 Glu Glu Lys Ile Pro Ser Leu Ile Lys Thr Leu Gln Asn Lys Leu 1565 1570 1575 Cys Ser Lys Phe Thr Arg Gly Ala Gln Lys Leu Leu Ser Glu Ala 1580 1585 1590 Ile Asn Lys Ser Ala Phe Gln Ser Cys Val Ser Ser Gly Phe Ile 1595 1600 1605 Gly Leu Cys Lys Thr Leu Gly Ser Arg Cys Val Arg Asn Lys Asn 1610 1615 1620 Arg Glu Asn Met Tyr Ile Arg Lys Val Leu Glu Asp Leu Thr Met 1625 1630 1635 Asp Glu His Val Thr Arg Val His Lys Gln Asp Gly Val Met Leu 1640 1645 1650 Tyr Ile Cys Asp Lys Gln Arg His Pro Glu Ala His Arg Asp His 1655 1660 1665 Ile Asn Leu Leu Arg Pro Leu Leu Trp Asp Tyr Ile Cys Ile Ser 1670 1675 1680 Leu Ser Asn Ser Phe Glu Leu Gly Val Trp Val Leu Ala Glu Pro 1685 1690 1695 Val Lys Gly Lys Asn Glu Ser Asn Ser Ala Val Arg His Leu Asn 1700 1705 1710 Pro Cys Asp Tyr Val Ala Arg Lys Pro Glu Ser Ser Arg Leu Leu 1715 1720 1725 Glu Asp Lys Val Ser Leu Asn His Val Ile Gln Ser Val Arg Arg 1730 1735 1740 Leu Tyr Pro Lys Ile Phe Glu Asp Gln Leu Leu Pro Phe Met Phe 1745 1750 1755 Asp Val Ser Ser Lys Asn Met Arg Trp Ser Pro Arg Ile Lys Phe 1760 1765 1770 Leu Asp Leu Cys Val Leu Ile Asp Ile Asn Ser Glu Ser Leu Ser 1775 1780 1785 Leu Ile Ser His Val Val Lys Trp Lys Arg Asp Glu His Tyr Thr 1790 1795 1800 Val Leu Phe Ser Asp Leu Val Asn Ser His Gln Arg Ser Asp Ser 1805 1810 1815 Ser Leu Val Asp Glu Phe Val Val Ser Thr Arg Asp Val Cys Lys 1820 1825 1830 Asn Phe Leu Lys Gln Val Tyr Phe Glu Ser Phe Val Arg Glu Phe 1835 1840 1845 Val Ala Thr Ala Arg Thr Leu Gly Asn Phe Ser Trp Phe Pro His 1850 1855 1860 Lys Asp Met Met Pro Ser Glu Asp Gly Ala Glu Ala Leu Gly Pro 1865 1870 1875 Phe Gln Ser Phe Ile Leu Lys Val Val Asn Lys Lys Ile Glu Arg 1880 1885 1890 Pro Met Phe Arg Asn Asp Leu Gln Phe Gly Phe Gly Trp Phe Ser 1895 1900 1905 Tyr Arg Val Gly Asp Val Val Cys Asn Ala Ala Met Leu Ile Lys 1910 1915 1920 Gln Gly Leu Thr Asp Pro Lys Ala Phe Lys Ser Leu Arg Asp Leu 1925 1930 1935 Trp Asp Tyr Met Leu Ser Ser Thr Glu Gly Ile Leu Glu Phe Ser 1940 1945 1950 Ile Thr Val Asp Phe Thr His Asn Gln Asn Asn Thr Asp Cys Leu 1955 1960 1965 Arg Lys Phe Ser Leu Ile Phe Val Val Lys Cys Gln Leu Gln Ser 1970 1975 1980 Pro Gly Val Ala Asp Tyr Leu Ser Cys Ser His Phe Phe Lys Gly 1985 1990 1995 Glu Val Asp Arg Arg Leu Leu Asp Glu Cys Leu Asn Leu Leu Arg 2000 2005 2010 Thr Asp Pro Ile Phe Lys Ala Asn Asp Gly Val Phe Asp Ile Arg 2015 2020 2025 Ser Glu Glu Phe Glu Asp Tyr Met Glu Asp Pro Leu Thr Leu Gly 2030 2035 2040 Asp Ser Leu Glu Leu Glu Leu Ile Gly Ser Arg Arg Ile Leu Asn 2045 2050 2055 Glu Ile Lys Ser Thr Asp Phe Glu Arg Ile Gly Pro Glu Trp Glu 2060 2065 2070 Pro Val Pro Leu Thr Ile Arg Lys Gly Ala Leu Phe Glu Gly Arg 2075 2080 2085 Asn Phe Val Gln Asn Ile Ser Val Lys Leu Glu Thr Lys Asp Met 2090 2095 2100 Arg Val Phe Leu Ala Glu Leu Glu Gly Cys Gly Lys Ile Gly Asp 2105 2110 2115 Val Leu Gly Ser Leu Leu Leu His Arg Phe Arg Thr Gly Glu His 2120 2125 2130 Leu Met Glu Ser Glu Ile Ser Thr Val Leu Gln Glu Leu Cys Met 2135 2140 2145 Asp Arg Ser Val Met Leu Thr Pro Leu Ser Phe Val Pro Asp Trp 2150 2155 2160 Phe Thr Phe Arg Asp Cys Arg Leu Cys Phe Ser Arg Ser Lys Asn 2165 2170 2175 Thr Val Met Tyr Glu Thr Thr Gly Gly Arg Phe Arg Leu Lys Gly 2180 2185 2190 Lys Ser Cys Asp Asp Trp Leu Ala Glu Arg Val Ala Glu Glu Ile 2195 2200 2205 Asp <210> 8 <211> 6630 <212> DNA <213> Lymphocytic choriomeningitis virus <220> <221> MISC_FEATURE <223> Lymphocytic choriomeningitis virus wild-type L-protein; ssRNA Amphisone-stranded virus; Arenaviridae; Arenavirus; Old World Arenavirus <400> 8 atggatgaaa ctattgcaga tttgagagag ttgtgtctaa attacataga acaggacgag 60 aggctgtcaa ggcaaaaact caacttcctg ggacaaagag aacccagaat ggtgctaatt 120 gagggactca aattgttatc acgctgtata gagatagaca gtgcagacaa aagtggttgc 180 atacacaacc acgatgacaa atctgttgaa acaatcctaa tagactctgg gattgtgtgt 240 ccaggactgc cactcatcat ccctgatggt tataagttga ttgacaattc ccttattctt 300 cttgaatgtt ttgttagaag cacaccagct agttttgaaa agaagttcat tgaggacacc 360 aacaaactag catgcatcaa agaagatctt gctgttgcag gcatcacact ggttccaata 420 gtggatggtc gttgtgatta tgataacagt ttcatgccag aatgggtgaa ttttaagttc 480 agagacctcc tatttaaact cctggagtat tctagtcaag atgagaaagt ttttgaggag 540 tctgaatact tcaggctctg tgagtctctt aagaccactg ttgacaaacg ttccggcatg 600 gactcaatga aaattttgaa agacgcaaga tcatttcata acgatgagat tatgaaaatg 660 tgccacgatg gtgtcaaccc caacatgagt tgcgatgatg tggtctttgg cataaattcc 720 tttttggca ggtttaggag ggacctgtta aatgggaaac tcaaaaggaa tttccaaaag 780 gtcagccctg ggggcttaat caaggaattc tctgaacttt atgaaaccct tactgataat 840 gatgacatat taatgttgag caaagaggca gttgaatcct gccccttaat gaggttcatt 900 960 ctctctatgt tgaacaaggt gaaaagttta aaattattaa acactagaag gagacagctg 1020 ctgaacttag atgtcttatg tctttcttca cttattaagc agtcaatttc caaagggttg 1080 gaaaatgata aacattgggt tggttgttgc tacagtagtg tgaatgatag gcttgtgagc 1140 cttcaaagta ccaaagaaga attcatgaga cttttgaaga acagaagaaa atcaagagtg 1200 cacaaaaagg catctcttga tgagcttttt agggtatcca taaatgagtt catagcaaaa 1260 atccagaaat gcctatcaac agtgggactt agttttgagc attacggact atcagaatgc 1320 ctcgtgcaag aatgccatat accatttgct gaatttgaga actttatgag agccgggact 1380 catcctgtaa tgcattacac aaaatttgaa gattacactt tccagcctaa catagagcaa 1440 ttgaggggtt tacagagttt gagaaaactg tcatctgttt gtttggctct aacaaacagc 1500 atgaaaacaa gctcagttgc aaggttgaga cagaaccaac tggggtctgt gagatatcaa 1560 gtggtggagt gcaaagaggt gttttgccag ataataaaac tggattccga agagtatcat 1620 ctactatatc agaaaactgg agaatcatcg aggtgttatt ccatacaagg tccggatggt 1680 cacttgattt ccttttacgc agatccaaaa aggttctttt taccaattttt ttcagatgag 1740 gtgttgcaca acatgataga cacaatgatt tcatggatta ggtcatgccc tgacttaaaa 1800 gattctctta ttgacattga gactgcacta aggacattga tcctactgat gctcaccaac 1860 ccaacaaaga gaaatcaaaa gcaggttcaa aatattaggt atttagtgat ggccatcgtc 1920 tcagacttt catcgacctc attaatggat aagttgaagg aggatctaat cacacctgcc 1980 gagaaagtgg tgtacaggct gcttcggttt ttgattagga caatttttgg tactggtgaa 2040 aaggtgttat tgagtgcaaa attcaagttt atgttgaatg tgtcatacct gtgtcatttg 2100 atcacaaagg agacccctga tagattgaca gatcagataa aatgttttga aaagttcttt 2160 gagcccaaga gtgagtttgg tttctttgtc aaccctaagg aaacaatcac acccgaagag 2220 gaatgtgttt tttatgaaca aatgaagaag ttcaccggta aagatattga ttgtcagcat 2280 tcaacccctg gtgttaattt agagatcttt agcatgatgg tatcttcatt caacaatggc 2340 accttaattc taaaagggga gaaaaggctc aacaatctgg accccacatgac caactctgga 2400 tgtgcgacag cattagatct cgcaagcaac aaaagtgtgg ttgtcaataa acatctgaat 2460 ggagaacggc ttttggagta tgattttaac aaattgcttg ttagtgctgt gagccaaatt 2520 acagagggct tcatgaggaa acaaaagtat aagctgagac actcagatta cgaatataag 2580 gtctcaaagc ttgtctctag attagtcatc ggttccagga aaacagaagt agacaaattg 2640 gaagatgatc cggtagatgt gtgtttcgag ggggaggagg agacaagttt tttcaggagt 2700 ttagaagata aggtcagctc cacaataaca cggtataata gaggcactag gcttaatgaa 2760 gggcaagggg agggagaatt caagaacaca aaaggactac accaccttca gattattttg 2820 tcaggtaaaa gagcttatct gaggaaagtc attttatcag aaatttcatt tcatctagta 2880 gaggactttg atccatcctg tctcaccaat gacgacatga ggtttatttg tgaggctgtt 2940 gaaggttcaa cagaactgtc accattgtat tttacatcag ctgtcaaaga acaatgtggt 3000 ctggatgaga tggcaagaaa cctctgtaga aagttcttct cagagggtga ttggttctca 3060 tgtatgaaga tgatcttgtt acagatgaat gcaaatgcgt attcagggaa gtacagacac 3120 atgcagaggc agagcttaaa ttttaaattt gactgggaca aattggaaga agatgtaaga 3180 attagtgaaa gggaaagcaa ttctgaatct ctaagtaagg ccctttcatt gacaaaatgc 3240 atgagtgctg ctctaaagaa tctgtgtttt tactcagaag aatcaccaac atcatacact 3300 tcagttggcc ctgactctgg gagactaaaa tttgcattgt catacaaaga gcaggttggg 3360 ggaatagag agctttacat tggggatttg aggacaaaaa tgttcacaag attggtagaa 3420 gattattttg aatccttttc tagtttcttt tcaggatctt gtttaaacaa tgacaaagag 3480 tttgaaaatg caatcttgtc aatgactatc aatgtgagag aagggttgtt aaactacagc 3540 atggatcaca gcaaatgggg accaatgatg tgcccattcc tattcttaat gcttctccaa 3600 aatctcaaac tgggtgatga tcagtacgtg cgttctggaa aagatcatgt tagcaccttg 3660 ttgacttggc atatgcataa acttgttgaa gtccctttcc ctgttgtgaa tgcaatgatg 3720 aaatcatatg ttaaatcaaa actcaagctt ctcaaagggt caggaacgac tgttacggag 3780 agaatcttta gagagtattt tgaaatgggg gtggtgccat ctcacatatc tagtctcatt 3840 gacatgggac aggggatcct acacaatgct tctgattttt acggtttaat tagtgaaagg 3900 tttatcaatt attgtattgg tgtcattttt ggagagaggc cagaagccta tacatcaagt 3960 gatgatcaga tcactttatt tgacaagaga ttgagtgact tagttgatag tgacccagaa 4020 gaagtccttg tcttgctgga attccactct cacttaagtg gtttgttgaa caagttcatc 4080 agtccaaaaa gtgtggttgg gcggtttgca gcggaattca aatccagatt ttatgtgtgg 4140 ggggaggagg tccctctcct cacgaaattt gtgtctgcgg cactacacaa tgttaagtgt 4200 aaagaaccgc atcaactttg tgagacaata gatacgattg ctgatcaagc tatagcaaat 4260 ggagttccag ttttttagt aaactgtatc cagaggagga cactggatct cttgaaatat 4320 gctaatttcc ctttagatcc attcttgtta aacactcaca ctgatgtaaa ggattggtta 4380 gatggttcta gaggttatag aatccaaaga ctcattgaag aattgtgtcc cagtgaaaca 4440 aagatcatga gaaaacttgt aagaagacta catcacaaac tcaagaacgg tgaatgtaac 4500 gaggaattt ttctagacct cttcaacagg gaaaagaaag aggccatcct tcaattggga 4560 gagattcttg gtcttgagga tgatcttaat gagttggcaa gcatcaattg gttgaatctg 4620 aatgaaatgt tcccattgag gatggttctg agacaaaaag tggtttaccc atcagtaatg 4680 acctttcaag aggaaaagat cccctcattg attaaaacac tccaaaataa gctttgtagt 4740 aagttcacaa gaggtgcaca gaagctgttg tcagaggcaa tcaacaaatc agcttttcag 4800 agttgtgtct catccggctt tataggtctc tgtaagactt taggaagtag gtgtgtgaga 4860 aataaaaaca gggaaaatat gtatatcaga aaggtgcttg aagatctgac catggatgaa 4920 catgtcacaa gggttcacaa acaagatggt gtgatgttgt acatttgcga caagcagaga 4980 cacccagagg ctcaccgtga ccacatcaac cttttgaggc cccttctctg ggactacatt 5040 tgcatctcat tgagcaactc ttttgagctg ggtgtttggg ttttagcaga acctgtgaaa 5100 ggaaagaacg agagtaattc ggctgttagg cacttaaatc catgtgatta tgtagcaaga 5160 aaacctgaga gttcgagact actagaggat aaagtgagtt tgaatcatgt aattcaatct 5220 gtgaggcgac tgtaccccaa aatctttgag gatcagttgc tcccattcat gtctgatgtg 5280 agctcaaaaa atatgagatg gagtcccagg attaaattcc ttgacctttg tgtgctgatt 5340 gacatcaact cagagtcttt gtcactcatt tctcatgttg tcaaatggaa gagggacgaa 5400 cattacactg tgctgttttc tgatctcgtc aactctcacc aacggtcaga ctcaagttta 5460 gttgatgaat ttgttgtcag cacaagggat gtctgcaaga actttttgaa gcaagtgtat 5520 ttcgaatcat ttgtacgaga gtttgttgca acagctagga ccttaggtaa cttttcatgg 5580 ttcccccata aggacatgat gccatctgaa gatggcgctg aagcactggg acccttccaa 5640 tcatttatt tgaaagtggt gaacaagaaa atagagaggc ccatgtttag gaatgacttg 5700 cagtttggtt ttggttggtt ccttatcgt gtgggggatg ttgtgtgtaa tgccgctatg 5760 ttaattaagc agggtttgac agatccaaaa gcatttaaat ctttaagaga tttgtgggat 5820 tacatgctca gcagcacaga ggggatattg gagttctcaa tcacagtgga tttcacacac 5880 aaccagaaca acactgactg cttgaggaaa ttttcattga tctttgtggt taaatgccaa 5940 ttacagagtc caggtgtagc tgattactta tcgtgctctc atttcttcaa aggtgaggtt 6000 gacaggagat tattagatga gtgtctcaat ctgttgagga cagaccccat cttaaagcg 6060 aatgatggag tctttgacat taggtctgaa gagtttgaag attacatgga agaccctttg 6120 acacttggtg attcactaga acttgaacta ataggttcta gaaggattct gaatgagatc 6180 aaatctactg actttgagag gatagggcct gagtgggaac ctgtgcctct gaccataagg 6240 aagggtgccc tctttgaggg gaggaacttt gttcagaata tctctgtgaa attggagaca 6300 aaggacatga gggtctttct ggcagagctc gagggctgtg gaaaaattgg tgatgtcctc 6360 ggcagcctcc tcctgcaccg attcagaact ggtgagcact tgatggagtc agaaataagt 6420 acagttcttc aggagctctg catggacaga tccgtcatgc tgacaccatt atcttttgtg 6480 ccagattggt tcaccttcag agattgtagg ctctgcttca gcaggtcaaa gaacactgta 6540 atgtatgaga caactggggg caggttcaga ctcaagggga aatcctgtga cgattggctg 6600 gcggagcggg tggccgagga gatcgactag 6630 <210> 9 <211> 1497 <212> DNA <213> Lymphocytic choriomeningitis virus (strain WE) <400> 9 atgggtcaga ttgtgacaat gtttgaggct ttgcctcaca tcattgatga ggtcatcaac 60 attgtcatta ttgtgctcat tataatcacg agcatcaaag ctgtgtacaa tttcgccacc 120 tgtgggatat tagcactggt cagcttcctt tttttggctg gtaggtcctg tggcatgtac 180 ggccttaatg gtcccgacat ctataaaggg gtttaccagt tcaaatcagt ggagtttgat 240 atgtctcact taaatctgac gatgcccaat gcgtgctcag ccaacaactc tcatcactac 300 atcagtatgg gaagctctgg actggagcta actttcacta acgactccat ccttaatcac aatttttgca acttaacctc cgctttcaac aaaaaagactt ttgaccatac actcatgagt atagtctcga gtctgcacct cagtattaga gggaattcca accacaaagc agtgtcttgt 540. gattttaaca atggcatcac cattcaatac aacttgtcat tttcggaccc acagagcgct ataagccagt gtaggacttt cagaggtaga gtcttggaca tgtttagaac tgcctttgga ggaaataca tgagaagtgg ctggggctgg gcaggttcag atggcaagac cacttggtgc agccaaacaa gctatcagta cctaatcata caaacagga cttgggaaaa ccactgtaga tatgcaggcc cttttgggat gtctagaatc ctctttgctc aggaaaagac aaagtttctc actaggagac ttgcaggcac attcacctgg accctgtcag actcctcagg agtagaaaat ccaggtggtt attgcctgac caaatggatg atccttgctg cagagctcaa atgttttggg aatacagctg ttgcaaaatg taatgtcaat catgatgaag agttctgtga catgctacga ctaattgatt acaacaaggc cgccctgagt aagttcaagc aagatgtaga gtctgccttg catgtattca aaacaacagt aaattcttg atttccgatc agctgttgat gaggaatcat 1080 ctaagagatc taatgggggt accatactgt aattactcaa agttctggta tctggaacat 1140 gctaagactg gtgagactag tgtacccaag tgctggcttg tcactaatg ctcctacttg 1200 aatgagacccc actttagtga tcaaatcgaa caagaagcag ataacatgat cacagagatg 1260 ttgaggaagg actacataaa aagacaaggg agtactcctt tagccttaat ggatcttttg 1320 atgttttcaa catcagcata tctaatcagc atctttctgc atcttgtgaa gataccaaca 1380 catagacaca taaagggcgg ttcatgtcca aagccacacc gcttgaccaa caaggggatc 1440 tgtagttgtg gtgcattcaa ggtgcctggt gtaaaaacta tctggaaaag acgctga 1497 <210> 10 <211> 498 <212> PRT <213> Connect to the Website (WE) <400> 10 Met Gly Gln Ile Val Thr Met Phe Glu Ala Leu Pro His Ile Ile Asp 1 5 10 15 Glu Val Ile Asn Ile Val Ile Ile Val Leu Ile Ile Thr Ser Ile 20 25 30 Lys Ala Val Tyr Asn Phe Ala Thr Cys Gly Ile Leu Ala Leu Val Ser 35 40 45 Phe Leu Phe Leu Ala Gly Arg Ser Cys Gly Met Tyr Gly Leu Asn Gly 50 55 60 Pro Asp Ile Tyr Lys Gly Val Tyr Gln Phe Lys Ser Val Glu Phe Asp 65 70 75 80 Met Ser His Leu Asn Leu Thr Met Pro Asn Ala Cys Ser Ala Asn Asn 85 90 95 Ser His His Tyr Ile Ser Met Gly Ser Ser Gly Leu Glu Leu Thr Phe 100 105 110 Thr Asn Asp Ser Ile Leu Asn His Asn Phe Cys Asn Leu Thr Ser Ala 115 120 125 Phe Asn Lys Lys Thr Phe Asp His Thr Leu Met Ser Ile Val Ser Ser 130 135 140 Leu His Leu Ser Ile Arg Gly Asn Ser Asn His Lys Ala Val Ser Cys 145 150 155 160 Asp Phe Asn Asn Gly Ile Thr Ile Gln Tyr Asn Leu Ser Phe Ser Asp 165 170 175 Pro Gln Ser Ala Ile Ser Gln Cys Arg Thr Phe Arg Gly Arg Val Leu 180 185 190 Asp Met Phe Arg Thr Ala Phe Gly Gly Lys Tyr Met Arg Ser Gly Trp 195 200 205 Gly Trp Ala Gly Ser Asp Gly Lys Thr Thr Trp Cys Ser Gln Thr Ser 210 215 220 Tyr Gln Tyr Leu Ile Ile Gln Asn Arg Thr Trp Glu Asn His Cys Arg 225 230 235 240 Tyr Ala Gly Pro Phe Gly Met Ser Arg Ile Leu Phe Ala Gln Glu Lys 245 250 255 Thr Lys Phe Leu Thr Arg Arg Leu Ala Gly Thr Phe Thr Trp Thr Leu 260 265 270 Ser Asp Ser Ser Gly Val Glu Asn Pro Gly Gly Tyr Cys Leu Thr Lys 275 280 285 Trp Met Ile Leu Ala Ala Glu Leu Lys Cys Phe Gly Asn Thr Ala Val 290 295 300 Ala Lys Cys Asn Val Asn His Asp Glu Glu Phe Cys Asp Met Leu Arg 305 310 315 320 Leu Ile Asp Tyr Asn Lys Ala Ala Leu Ser Lys Phe Lys Gln Asp Val 325 330 335 Glu Ser Ala Leu His Val Phe Lys Thr Thr Val Asn Ser Leu Ile Ser 340 345 350 Asp Gln Leu Leu Met Arg Asn His Leu Arg Asp Leu Met Gly Val Pro 355 360 365 Tyr Cys Asn Tyr Ser Lys Phe Trp Tyr Leu Glu His Ala Lys Thr Gly 370 375 380 Glu Thr Ser Val Pro Lys Cys Trp Leu Val Thr Asn Gly Ser Tyr Leu 385 390 395 400 Asn Glu Thr His Phe Ser Asp Gln Ile Glu Gln Glu Ala Asp Asn Met 405 410 415 Ile Thr Glu Met Leu Arg Lys Asp Tyr Ile Lys Arg Gln Gly Ser Thr 420 425 430 Pro Leu Ala Leu Met Asp Leu Leu Met Phe Ser Thr Ser Ala Tyr Leu 435 440 445 Ile Ser Ile Phe Leu His Leu Val Lys Ile Pro Thr His Arg His Ile 450 455 460 Lys Gly Gly Ser Cys Pro Lys Pro His Arg Leu Thr Asn Lys Gly Ile 465 470 475 480 Cys Ser Cys Gly Ala Phe Lys Val Pro Gly Val Lys Thr Ile Trp Lys 485 490 495 Arg Arg <210> 11 <211> 1677 <212> DNA <213> Lymphocytic choriomeningitis virus (strain WE) <400> 11 atgtctttgt ccaaagaagt caaaagcttt cagtggacac aggcgttgag gagggagttg 60 cagagtttta catcagatgt aaaggctgcc gtcatcaagg acgcaaccag tcttctaaat 120 gggttggact tttctgaagt cagcaacgtt cagaggatca tgagaaagga aaggagggat 180 gataaagact tgcagagact caggagtctt aaccagactg tgcattctct tgttgatctg 240 aagtctacat caaagaaaaa tgttctgaaa gtgggaagac ttagtgcaga ggaattgatg 300 acccttgcag ctgatcttga gaagctgaag gccaaaatta tgagaactga gaggcctcaa 360 gcttctggag tctacatggg aaatttgaca gcacaacaac ttgatcaaag atcccaaata 420 ctgcaaatgg ttgggatgag aagacctcag cagggtgcaa gtggtgtagt aagggtttgg 480 gatgtgaagg actcatcact tctgaacaat cagttcggca caatgccaag cctgacaatg 540 gcttgcatgg caaaacagtc acagacccca ctcaatgatg ttgtgcaggc actcacagac 600 cttggcttac tttacacagt caaatacccg aatctcagtg atcttgaaag gctaaaggat 660 aaacacccag ttctgggggt cattactgaa cagcaatcta gtatcaatat ctctggttat 720 aatttcagtc ttggtgcagc tgtgaaagcg ggggcagctc tgctagatgg agggaacatg 780 ctggaatcta tcttgatcaa accgagcaac agtgaggatc tcctaaaagc agtctcggg 840 gccaagaaga aactcaacat gtttgtctca gatcaagttg gagatagaaa tccctatgaa 900 aacatccttt ataaagtctg tctttcaggt gaaggatggc catacatagc ctgtagaacg 960 tcagttgtgg ggagagcatg ggagaacaca acaattgatc tcacaaatga aaaacttgtt 1020 gccaactcat ctaggccagt gcctggagca gcaggcccac ctcaggtggg cttgagttac 1080 agtcagacaa tgctgttgaa agacttgatg ggagggattg atcccaatgc tcccacatgg 1140 attgacattg agggcaggtt caatgatcca gtggagatag caatattcca accacaaaat 1200 gggcaattca tacattttta cagggaacct acggaccaga agcaattcaa gcaggactca 1260 aagtattcac acggcatgga tcttgctgat ctcttcaatg cacagcctgg gctgacctca 1320 tcagttatag gtgctctccc acaagggatg gttttgagct gtcaaggttc tgatgacatc 1380 agaaagcttc tggactcaca aaatagaagg gacataaaac tcattgatgt tgagatgacc 1440 aaggaggcct caagagaata tgaagataaa gtgtgggaca aatatggctg gctatgcaaa 1500 atgcacactg gggtagtgag agacaaaaag aagaaagaga tcaccccaca ctgtgcactc 1560 atggactgca tcatttttga gagtgcttcc aaggcaagac tccctgatct aaaaaccgtt 1620 cacaacatcc tgccacatga tttaatcttc agaggaccca atgttgtgac actctaa 1677 <210> 12 <211> 558 <212> PRT <213> Lymphocytic choriomeningitis virus (strain WE) <400> 12 Met Ser Leu Ser Lys Glu Val Lys Ser Phe Gln Trp Thr Gln Ala Leu 1 5 10 15 Arg Arg Glu Leu Gln Ser Phe Thr Ser Asp Val Lys Ala Ala Val Ile 20 25 30 Lys Asp Ala Thr Ser Leu Leu Asn Gly Leu Asp Phe Ser Glu Val Ser 35 40 45 Asn Val Gln Arg Ile Met Arg Lys Glu Arg Arg Asp Asp Lys Asp Leu 50 55 60 Gln Arg Leu Arg Ser Leu Asn Gln Thr Val His Ser Leu Val Asp Leu 65 70 75 80 Lys Ser Thr Ser Lys Lys Asn Val Leu Lys Val Gly Arg Leu Ser Ala 85 90 95 Glu Glu Leu Met Thr Leu Ala Ala Asp Leu Glu Lys Leu Lys Ala Lys 100 105 110 Ile Met Arg Thr Glu Arg Pro Gln Ala Ser Gly Val Tyr Met Gly Asn 115 120 125 Leu Thr Ala Gln Gln Leu Asp Gln Arg Ser Gln Ile Leu Gln Met Val 130 135 140 Gly Met Arg Arg Pro Gln Gln Gly Ala Ser Gly Val Val Arg Val Trp 145 150 155 160 Asp Val Lys Asp Ser Ser Leu Leu Asn Asn Gln Phe Gly Thr Met Pro 165 170 175 Ser Leu Thr Met Ala Cys Met Ala Lys Gln Ser Gln Thr Pro Leu Asn 180 185 190 Asp Val Val Gln Ala Leu Thr Asp Leu Gly Leu Leu Tyr Thr Val Lys 195 200 205 Tyr Pro Asn Leu Ser Asp Leu Glu Arg Leu Lys Asp Lys His Pro Val 210 215 220 Leu Gly Val Ile Thr Glu Gln Gln Ser Ser Ile Asn Ile Ser Gly Tyr 225 230 235 240 Asn Phe Ser Leu Gly Ala Ala Val Lys Ala Gly Ala Ala Leu Leu Asp 245 250 255 Gly Gly Asn Met Leu Glu Ser Ile Leu Ile Lys Pro Ser Asn Ser Glu 260 265 270 Asp Leu Leu Lys Ala Val Leu Gly Ala Lys Lys Lys Leu Asn Met Phe 275 280 285 Val Ser Asp Gln Val Gly Asp Arg Asn Pro Tyr Glu Asn Ile Leu Tyr 290 295 300 Lys Val Cys Leu Ser Gly Glu Gly Trp Pro Tyr Ile Ala Cys Arg Thr 305 310 315 320 Ser Val Val Gly Arg Ala Trp Glu Asn Thr Thr Ile Asp Leu Thr Asn 325 330 335 Glu Lys Leu Val Ala Asn Ser Ser Arg Pro Val Pro Gly Ala Ala Gly 340 345 350 Pro Pro Gln Val Gly Leu Ser Tyr Ser Gln Thr Met Leu Leu Lys Asp 355 360 365 Leu Met Gly Gly Ile Asp Pro Asn Ala Pro Thr Trp Ile Asp Ile Glu 370 375 380 Gly Arg Phe Asn Asp Pro Val Glu Ile Ala Ile Phe Gln Pro Gln Asn 385 390 395 400 Gly Gln Phe Ile His Phe Tyr Arg Glu Pro Thr Asp Gln Lys Gln Phe 405 410 415 Lys Gln Asp Ser Lys Tyr Ser His Gly Met Asp Leu Ala Asp Leu Phe 420 425 430 Asn Ala Gln Pro Gly Leu Thr Ser Ser Val Ile Gly Ala Leu Pro Gln 435 440 445 Gly Met Val Leu Ser Cys Gln Gly Ser Asp Asp Ile Arg Lys Leu Leu 450 455 460 Asp Ser Gln Asn Arg Arg Asp Ile Lys Leu Ile Asp Val Glu Met Thr 465 470 475 480 Lys Glu Ala Ser Arg Glu Tyr Glu Asp Lys Val Trp Asp Lys Tyr Gly 485 490 495 Trp Leu Cys Lys Met His Thr Gly Val Val Arg Asp Lys Lys Lys Lys 500 505 510 Glu Ile Thr Pro His Cys Ala Leu Met Asp Cys Ile Ile Phe Glu Ser 515 520 525 Ala Ser Lys Ala Arg Leu Pro Asp Leu Lys Thr Val His Asn Ile Leu 530 535 540 Pro His Asp Leu Ile Phe Arg Gly Pro Asn Val Val Thr Leu 545 550 555 <210> 13 <211> 273 <212> DNA <213> Lymphocytic choriomeningitis virus (strain WE) <400> 13 atgggccaag gcaagtccaa agaagaaagg gacaccagca atacaggcag agcagagctt 60 ttgccagaca ccacctatct tggtcctcta aattgtaaat catgttggca gaaatttgac 120 agcttggtta gatgccatga ccactatctt tgcagacact gtctgaatct cctgctgtca 180 gtttccgaca gatgtcctct ctgtaagtat ccactgccaa ccaaactgaa ggtgtcaaca 240 gtcccaagct ccccacctcc ctatgaggag tga 273 <210> 14 <211> 90 <212> PRT <213> Lymphocytic choriomeningitis virus (strain WE) <400> 14 Met Gly Gln Gly Lys Ser Lys Glu Glu Arg Asp Thr Ser Asn Thr Gly 1 5 10 15 Arg Ala Glu Leu Leu Pro Asp Thr Thr Tyr Leu Gly Pro Leu Asn Cys 20 25 30 Lys Ser Cys Trp Gln Lys Phe Asp Ser Leu Val Arg Cys His Asp His 35 40 45 Tyr Leu Cys Arg His Cys Leu Asn Leu Leu Leu Ser Val Ser Asp Arg 50 55 60 Cys Pro Leu Cys Lys Tyr Pro Leu Pro Thr Lys Leu Lys Val Ser Thr 65 70 75 80 Val Pro Ser Ser Pro Pro Pro Tyr Glu Glu 85 90 <210> 15 <211> 6630 <212> DNA <213> lymphocytic lymphoma virus <400> 15 atggatgaaa ctattgcaga tttgagagag ttgtgtctaa attacataga acaggacgag 60 aggctgtcaa ggcaaaaact caacttcctg ggacaaagag aacccagaat ggtgctaatt 120 gagggactca aattgttatc acgctgtata gagagaca gtgcagacaa aagtggttgc 180 atacacaacc acgatgacaa atctgttgaa acaatcctaa tagactctgg gattgtgtgt 240 ccaggactgc cactcatcat ccctgatggt tataagttga ttgacaattc ccttatctt 300 cttgaatgtt ttgttagaag cacaccagct agttttgaaa agaagttcat tgaggacacc 360 aacaaactag catgcatcaa agaagatctt gctgttgcag gcatcacact ggttccaata 420 gtggatggtc gttgtgatta tgataacagt ttcatgccag aatgggtgaa ttttaagttc 480 agagacctcc tatttaaact cctggagtat tctagtcaag atgagaaagt ttttgaggag 540 tctgaatact tcaggctctg tgagtctctt aagaccactg ttgacaaacg ttccggcatg 600 gactcaatga aaattttgaa agacgcaaga tcatttcata acgatgagat tatgaaaatg 660 tgccacgatg gtgtcaaccc caacatgagt tgcgatgatg tggtctttgg cataaattcc 720 tttttggca ggtttaggag ggacctgtta aatgggaaac tcaaaaggaa tttccaaaag 780 gtcagccctg ggggcttaat caaggaattc tctgaacttt atgaaaccct tactgataat 840 gatgacatat taatgttgag caaagaggca gttgaatcct gccccttaat gaggttcatt 900 960 ctctctatgt tgaacaaggt gaaaagttta aaattattaa acactagaag gagacagctg 1020 ctgaacttag atgtcttatg tctttcttca cttattaagc agtcaatttc caaagggttg 1080 gaaaatgata aacattgggt tggttgttgc tacagtagtg tgaatgatag gcttgtgagc 1140 cttcaaagta ccaaagaaga attcatgaga cttttgaaga acagaagaaa atcaagagtg 1200 cacaaaaagg catctcttga tgagcttttt agggtatcca taaatgagtt catagcaaaa 1260 atccagaaat gcctatcaac agtgggactt agttttgagc attacggact atcagaatgc 1320 ctcgtgcaag aatgccatat accatttgct gaatttgaga actttatgag agccgggact 1380 catcctgtaa tgcattacac aaaatttgaa gattacactt tccagcctaa catagagcaa 1440 ttgaggggtt tacagagttt gagaaaactg tcatctgttt gtttggctct aacaaacagc 1500 atgaaaacaa gctcagttgc aaggttgaga cagaaccaac tggggtctgt gagatatcaa 1560 gtggtggagt gcaaagaggt gttttgccag ataataaaac tggattccga agagtatcat 1620 ctactatatc agaaaactgg agaatcatcg aggtgttatt ccatacaagg tccggatggt 1680 cacttgattt ccttttacgc agatccaaaa aggttctttt taccaattttt ttcagatgag 1740 gtgttgcaca acatgataga cacaatgatt tcatggatta ggtcatgccc tgacttaaaa 1800 gattctctta ttgacattga gactgcacta aggacattga tcctactgat gctcaccaac 1860 ccaacaaaga gaaatcaaaa gcaggttcaa aatattaggt atttagtgat ggccatcgtc 1920 tcagactttt catcgacctc attaatggat aagttgaagg aggatctaat cacacctgcc 1980 gagaaagtgg tgtacaggct gcttcggttt ttgattagga caatttttgg tactggtgaa 2040 aaggtgttat tgagtgcaaa attcaagttt atgttgaatg tgtcatacct gtgtcatttg 2100 atcacaaagg agacccctga tagattgaca gatcagataa aatgttttga aaagttcttt 2160 gagcccaaga gtgagtttgg tttctttgtc aaccctaagg aaacaatcac acccgaagag 2220 gaatgtgttt tttatgaaca aatgaagaag ttcaccggta aagatattga ttgtcagcat 2280 tcaacccctg gtgttaattt agagatcttt agcatgatgg tatcttcatt caacaatggc 2340 accttaattc taaaagggga gaaaaggctc aacaatctgg accccacatgac caactctgga 2400 tgtgcgacag cattagatct cgcaagcaac aaaagtgtgg ttgtcaataa acatctgaat 2460 ggagaacggc ttttggagta tgattttaac aaattgcttg ttagtgctgt gagccaaatt 2520 acagagggct tcatgaggaa acaaaagtat aagctgagac actcagatta cgaatataag 2580 gtctcaaagc ttgtctctag attagtcatc ggttccagga aaacagaagt agacaaattg gaagatgatc cggtagtgt gtgtttcgag ggggaggagg agacaagttt tttcaggagt ttagaagata aggtcagctc cacaataca cggtataata gaggcactag gcttaatgaa gggcaagggg agggagaatt caagacaca aaaggactac accaccttca gattattttg tcaggtaaaa gagcttatct gaggaagtc attttatcag aaatttcatt tcatctagta gaggactttg atccatcctg tctcaccaat gacgacatga ggtttatttg tgaggctgtt gaggttcaa cagaactgtc accattgtat tttacatcag ctgtcaaaga acaatgtggt ctggatgaga tggcaagaaa cctctgtaga aagttcttct cagagggtga ttggttctca tgtatgaaga tgatcttgtt acagatgaat gcaaatgcgt attcagggaa gtacagacac atgcagaggc agagcttaaa ttttaaattt gactgggaca aattggaaga agatgtaaga attagtgaaa gggaaagcaa ttctgaatct ctaagtaagg ccctttcatt gacaaaatgc atgagtgctg ctctaaaga tctgtgtttt tactcagaag aatcaccaac atcatacact tcagttggcc ctgactctgg gagactaaaa tttgcattgt catacaaaga gcaggttggg 3360 ggaatagag agctttacat tggggatttg aggacaaaaa tgttcacaag attggtagaa 3420 gattattttg aatccttttc tagttcttt tcaggatctt gttaaacaa tgacaaagag 3480 tttgaaaatg caatcttgtc aatgactatc aatgtgagag aagggttgtt aaactacagc 3540 atggatcaca gcaaatgggg accaatgatg tgcccattcc tattcttaat gcttctccaa 3600 aatctcaaac tgggtgatga tcagtacgtg cgttctggaa aagatcatgt tagcaccttg 3660 ttgacttggc atatgcataa acttgttgaa gtccctttcc ctgttgtgaa tgcaatgatg 3720 aaatcatatg ttaaatcaaa actcaagctt ctcaaagggt caggaacgac tgttacggag 3780 agaatcttta gagagtattt tgaaatgggg gtggtgccat ctcacatatc tagtctcatt 3840 gacatgggac aggggatcct acacaatgct tctgattttt acggtttaat tagtgaaagg 3900 tttatcaatt attgtattgg tgtcattttt ggagagaggc cagaagccta tacatcaagt 3960 gatgatcaga tcactttatt tgacaagaga ttgagtgact tagttgatag tgacccagaa 4020 gaagtccttg tcttgctgga attccactct cacttaagtg gtttgttgaa caagttcatc 4080 agtccaaaaa gtgtggttgg gcggtttgca gcggaattca aatccagatt tttgtgtgg 4140 ggggaggagg tccctctcct cacgaaattt gtgtctgcgg cactacacaa tgttaagtgt 4200 aaagaaccgc atcaactttg tgagacaata gatacgattg ctgatcaagc tatagcaaat 4260 ggagttccag ttttttagt aaactgtatc cagaggagga cactggatct cttgaaatat 4320 gctaatttcc ctttagatcc attcttgtta aacactcaca ctgatgtaaa ggattggtta 4380 gatggttcta gaggttatag aatccaaaga ctcattgaag aattgtgtcc cagtgaaaca 4440 aagatcatga gaaaacttgt aagaagacta catcacaaac tcaagaacgg tgaatgtaac 4500 gaggaattt ttctagacct cttcaacagg gaaaagaaag aggccatcct tcaattggga 4560 gagattcttg gtcttgagga tgatcttaat gagttggcaa gcatcaattg gttgaatctg 4620 aatgaaatgt tcccattgag gatggttctg agacaaaaag tggtttaccc atcagtaatg 4680 acctttcaag aggaaaagat cccctcattg attaaaacac tccaaaataa gctttgtagt 4740 aagttcaaa gaggtgcaca gaagctgttg tcagaggcaa tcaacaaatc agcttttcag 4800 agttgtgtct catccggctt tataggtctc tgtaagactt taggaagtag gtgtgtgaga 4860 aataaaaaca gggaaaatat gtatatcaga aaggtgcttg aagatctgac catggatgaa 4920 4980 cacccagagg ctcaccgtga ccacatcaac cttttgaggc cccttctctg ggactacatt 5040 tgcatctcat tgagcaactc ttttgagctg ggtgtttggg ttttagcaga acctgtgaaa 5100 ggaagaacg agagtaattc gggctttagg cacttaaatc catgtgatta tgtagcaaga 5160 aaacctgaga gttcgagact actagaggat aaagtgagtt tgaatcatgt aattcaatct 5220 gtgaggcgac tgtaccccaa aatctttgag gatcagttgc tcccattcat gtctgatgtg 5280 agctcaaaaa atatgagatg gagtcccagg attaaattcc ttgacctttg tgtgctgatt 5340 5400 cattacactg tgctgttttc tgatctcgtc aactctcacc aacggtcaga ctcaagttta 5460 gttgatgaat ttgttgtcag cacaagggat gtctgcaaga actttttgaa gcaagtgtat 5520 ttcgaatcat ttgtacgaga gtttgttgca acagctagga ccttaggtaa cttttcatgg 5580 ttcccccata aggacatgat gccatctgaa gatggcgctg aagcactggg acccttccaa 5640 tcatttatt tgaaagtggt gaacaagaaa atagagaggc ccatgtttag gaatgacttg 5700 cagtttggtt ttggttggtt ccttatcgt gtgggggatg ttgtgtgtaa tgccgctatg 5760 ttaattaagc agggtttgac agatccaaaa gcatttaaat ctttaagaga tttgtgggat 5820 tacatgctca gcagcacaga ggggatattg gagttctcaa tcacagtgga tttcacacac 5880 aaccagaaca acactgactg cttgaggaaa ttttcattga tctttgtggt taaatgccaa 5940 ttacagagtc caggtgtagc tgattactta tcgtgctctc atttcttcaa aggtgaggtt 6000 gacaggagat tattagatga gtgtctcaat ctgttgagga cagaccccat cttaaagcg 6060 aatgatggag tctttgacat taggtctgaa gagtttgaag attacatgga agaccctttg 6120 acacttggtg attcactaga acttgaacta ataggttcta gaaggattct gaatgagatc 6180 aaatctactg actttgagag gatagggcct gagtgggaac ctgtgcctct gaccataagg 6240 aagggtgccc tctttgaggg gaggaacttt gttcagaata tctctgtgaa attggagaca 6300 aaggacatga gggtctttct ggcagagctc gagggctgtg gaaaaattgg tgatgtcctc 6360 ggcagcctcc tcctgcaccg attcagaact ggtgagcact tgatggagtc agaaataagt 6420 acagttcttc aggagctctg catggacaga tccgtcatgc tgacaccatt atcttttgtg 6480 ccagattggt tcaccttcag agattgtagg ctctgcttca gcaggtcaaa gaacactgta 6540 atgtatgaga caactggggg caggttcaga ctcaagggga aatcctgtga cgattggctg 6600 gcggagcggg tggccgagga gatcgactag 6630 <210> 16 <211> 2209 <212> PRT <213> Lymphocytic choriomeningitis virus (strain WE) <400> 16 Met Asp Glu Thr Ile Ala Asp Leu Arg Glu Leu Cys Leu Asn Tyr Ile 1 5 10 15 Glu Gln Asp Glu Arg Leu Ser Arg Gln Lys Leu Asn Phe Leu Gly Gln 20 25 30 Arg Glu Pro Arg Met Val Leu Ile Glu Gly Leu Lys Leu Leu Ser Arg 35 40 45 Cys Ile Glu Ile Asp Ser Ala Asp Lys Ser Gly Cys Ile His Asn His 50 55 60 Asp Asp Lys Ser Val Glu Thr Ile Leu Ile Asp Ser Gly Ile Val Cys 65 70 75 80 Pro Gly Leu Pro Leu Ile Ile Pro Asp Gly Tyr Lys Leu Ile Asp Asn 85 90 95 Ser Leu Ile Leu Leu Glu Cys Phe Val Arg Ser Thr Pro Ala Ser Phe 100 105 110 Glu Lys Lys Phe Ile Glu Asp Thr Asn Lys Leu Ala Cys Ile Lys Glu 115 120 125 Asp Leu Ala Val Ala Gly Ile Thr Leu Val Pro Ile Val Asp Gly Arg 130 135 140 Cys Asp Tyr Asp Asn Ser Phe Met Pro Glu Trp Val Asn Phe Lys Phe 145 150 155 160 Arg Asp Leu Leu Phe Lys Leu Leu Glu Tyr Ser Ser Gln Asp Glu Lys 165 170 175 Val Phe Glu Glu Ser Glu Tyr Phe Arg Leu Cys Glu Ser Leu Lys Thr 180 185 190 Thr Val Asp Lys Arg Ser Gly Met Asp Ser Met Lys Ile Leu Lys Asp 195 200 205 Ala Arg Ser Phe His Asn Asp Glu Ile Met Lys Met Cys His Asp Gly 210 215 220 Val Asn Pro Asn Met Ser Cys Asp Asp Val Val Phe Gly Ile Asn Ser 225 230 235 240 Phe Phe Gly Arg Phe Arg Arg Asp Leu Leu Asn Gly Lys Leu Lys Arg 245 250 255 Asn Phe Gln Lys Val Ser Pro Gly Gly Leu Ile Lys Glu Phe Ser Glu 260 265 270 Leu Tyr Glu Thr Leu Thr Asp Asn Asp Asp Ile Leu Met Leu Ser Lys 275 280 285 Glu Ala Val Glu Ser Cys Pro Leu Met Arg Phe Ile Thr Ala Glu Thr 290 295 300 His Gly His Glu Arg Gly Ser Asp Ala Asn Thr Glu Tyr Glu Arg Leu 305 310 315 320 Leu Ser Met Leu Asn Lys Val Lys Ser Leu Lys Leu Leu Asn Thr Arg 325 330 335 Arg Arg Gln Leu Leu Asn Leu Asp Val Leu Cys Leu Ser Ser Leu Ile 340 345 350 Lys Gln Ser Ile Ser Lys Gly Leu Glu Asn Asp Lys His Trp Val Gly 355 360 365 Cys Cys Tyr Ser Ser Val Asn Asp Arg Leu Val Ser Leu Gln Ser Thr 370 375 380 Lys Glu Glu Phe Met Arg Leu Leu Lys Asn Arg Arg Lys Ser Arg Val 385 390 395 400 His Lys Lys Ala Ser Leu Asp Glu Leu Phe Arg Val Ser Ile Asn Glu 405 410 415 Phe Ile Ala Lys Ile Gln Lys Cys Leu Ser Thr Val Gly Leu Ser Phe 420 425 430 Glu His Tyr Gly Leu Ser Glu Cys Leu Val Gln Glu Cys His Ile Pro 435 440 445 Phe Ala Glu Phe Glu Asn Phe Met Arg Ala Gly Thr His Pro Val Met 450 455 460 His Tyr Thr Lys Phe Glu Asp Tyr Thr Phe Gln Pro Asn Ile Glu Gln 465 470 475 480 Leu Arg Gly Leu Gln Ser Leu Arg Lys Leu Ser Ser Val Cys Leu Ala 485 490 495 Leu Thr Asn Ser Met Lys Thr Ser Ser Val Ala Arg Leu Arg Gln Asn 500 505 510 Gln Leu Gly Ser Val Arg Tyr Gln Val Val Glu Cys Lys Glu Val Phe 515 520 525 Cys Gln Ile Ile Lys Leu Asp Ser Glu Glu Tyr His Leu Leu Tyr Gln 530 535 540 Lys Thr Gly Glu Ser Ser Arg Cys Tyr Ser Ile Gln Gly Pro Asp Gly 545 550 555 560 His Leu Ile Ser Phe Tyr Ala Asp Pro Lys Arg Phe Phe Leu Pro Ile 565 570 575 Phe Ser Asp Glu Val Leu His Asn Met Ile Asp Thr Met Ile Ser Trp 580 585 590 Ile Arg Ser Cys Pro Asp Leu Lys Asp Ser Leu Ile Asp Ile Glu Thr 595 600 605 Ala Leu Arg Thr Leu Ile Leu Leu Met Leu Thr Asn Pro Thr Lys Arg 610 615 620 Asn Gln Lys Gln Val Gln Asn Ile Arg Tyr Leu Val Met Ala Ile Val 625 630 635 640 Ser Asp Phe Ser Ser Thr Ser Leu Met Asp Lys Leu Lys Glu Asp Leu 645 650 655 Ile Thr Pro Ala Glu Lys Val Val Tyr Arg Leu Leu Arg Phe Leu Ile 660 665 670 Arg Thr Ile Phe Gly Thr Gly Glu Lys Val Leu Leu Ser Ala Lys Phe 675 680 685 Lys Phe Met Leu Asn Val Ser Tyr Leu Cys His Leu Ile Thr Lys Glu 690 695 700 Thr Pro Asp Arg Leu Thr Asp Gln Ile Lys Cys Phe Glu Lys Phe Phe 705 710 715 720 Glu Pro Lys Ser Glu Phe Gly Phe Phe Val Asn Pro Lys Glu Thr Ile 725 730 735 Thr Pro Glu Glu Glu Cys Val Phe Tyr Glu Gln Met Lys Lys Phe Thr 740 745 750 Gly Lys Asp Ile Asp Cys Gln His Ser Thr Pro Gly Val Asn Leu Glu 755 760 765 Ile Phe Ser Met Met Val Ser Ser Phe Asn Asn Gly Thr Leu Ile Leu 770 775 780 Lys Gly Glu Lys Arg Leu Asn Asn Leu Asp Pro Met Thr Asn Ser Gly 785 790 795 800 Cys Ala Thr Ala Leu Asp Leu Ala Ser Asn Lys Ser Val Val Val Asn 805 810 815 Lys His Leu Asn Gly Glu Arg Leu Leu Glu Tyr Asp Phe Asn Lys Leu 820 825 830 Leu Val Ser Ala Val Ser Gln Ile Thr Glu Gly Phe Met Arg Lys Gln 835 840 845 Lys Tyr Lys Leu Arg His Ser Asp Tyr Glu Tyr Lys Val Ser Lys Leu 850 855 860 Val Ser Arg Leu Val Ile Gly Ser Arg Lys Thr Glu Val Asp Lys Leu 865 870 875 880 Glu Asp Asp Pro Val Asp Val Cys Phe Glu Gly Glu Glu Glu Thr Ser 885 890 895 Phe Phe Arg Ser Leu Glu Asp Lys Val Ser Ser Thr Ile Thr Arg Tyr 900 905 910 Asn Arg Gly Thr Arg Leu Asn Glu Gly Gln Gly Glu Gly Glu Phe Lys 915 920 925 Asn Thr Lys Gly Leu His His Leu Gln Ile Ile Leu Ser Gly Lys Arg 930 935 940 Ala Tyr Leu Arg Lys Val Ile Leu Ser Glu Ile Ser Phe His Leu Val 945 950 955 960 Glu Asp Phe Asp Pro Ser Cys Leu Thr Asn Asp Asp Met Arg Phe Ile 965 970 975 Cys Glu Ala Val Glu Gly Ser Thr Glu Leu Ser Pro Leu Tyr Phe Thr 980 985 990 Ser Ala Val Lys Glu Gln Cys Gly Leu Asp Glu Met Ala Arg Asn Leu 995 1000 1005 Cys Arg Lys Phe Phe Ser Glu Gly Asp Trp Phe Ser Cys Met Lys 1010 1015 1020 Met Ile Leu Leu Gln Met Asn Ala Asn Ala Tyr Ser Gly Lys Tyr 1025 1030 1035 Arg His Met Gln Arg Gln Ser Leu Asn Phe Lys Phe Asp Trp Asp 1040 1045 1050 Lys Leu Glu Glu Asp Val Arg Ile Ser Glu Arg Glu Ser Asn Ser 1055 1060 1065 Glu Ser Leu Ser Lys Ala Leu Ser Leu Thr Lys Cys Met Ser Ala 1070 1075 1080 Ala Leu Lys Asn Leu Cys Phe Tyr Ser Glu Glu Ser Pro Thr Ser 1085 1090 1095 Tyr Thr Ser Val Gly Pro Asp Ser Gly Arg Leu Lys Phe Ala Leu 1100 1105 1110 Ser Tyr Lys Glu Gln Val Gly Gly Asn Arg Glu Leu Tyr Ile Gly 1115 1120 1125 Asp Leu Arg Thr Lys Met Phe Thr Arg Leu Val Glu Asp Tyr Phe 1130 1135 1140 Glu Ser Phe Ser Ser Phe Phe Ser Gly Ser Cys Leu Asn Asn Asp 1145 1150 1155 Lys Glu Phe Glu Asn Ala Ile Leu Ser Met Thr Ile Asn Val Arg 1160 1165 1170 Glu Gly Leu Leu Asn Tyr Ser Met Asp His Ser Lys Trp Gly Pro 1175 1180 1185 Met Met Cys Pro Phe Leu Phe Leu Met Leu Leu Gln Asn Leu Lys 1190 1195 1200 Leu Gly Asp Asp Gln Tyr Val Arg Ser Gly Lys Asp His Val Ser 1205 1210 1215 Thr Leu Leu Thr Trp His Met His Lys Leu Val Glu Val Pro Phe 1220 1225 1230 Pro Val Val Asn Ala Met Met Lys Ser Tyr Val Lys Ser Lys Leu 1235 1240 1245 Lys Leu Leu Lys Gly Ser Gly Thr Thr Val Thr Glu Arg Ile Phe 1250 1255 1260 Arg Glu Tyr Phe Glu Met Gly Val Val Pro Ser His Ile Ser Ser 1265 1270 1275 Leu Ile Asp Met Gly Gln Gly Ile Leu His Asn Ala Ser Asp Phe 1280 1285 1290 Tyr Gly Leu Ile Ser Glu Arg Phe Ile Asn Tyr Cys Ile Gly Val 1295 1300 1305 Ile Phe Gly Glu Arg Pro Glu Ala Tyr Thr Ser Ser Asp Asp Gln 1310 1315 1320 Ile Thr Leu Phe Asp Lys Arg Leu Ser Asp Leu Val Asp Ser Asp 1325 1330 1335 Pro Glu Glu Val Leu Val Leu Leu Glu Phe His Ser His Leu Ser 1340 1345 1350 Gly Leu Leu Asn Lys Phe Ile Ser Pro Lys Ser Val Val Gly Arg 1355 1360 1365 Phe Ala Ala Glu Phe Lys Ser Arg Phe Tyr Val Trp Gly Glu Glu 1370 1375 1380 Val Pro Leu Leu Thr Lys Phe Val Ser Ala Ala Leu His Asn Val 1385 1390 1395 Lys Cys Lys Glu Pro His Gln Leu Cys Glu Thr Ile Asp Thr Ile 1400 1405 1410 Ala Asp Gln Ala Ile Ala Asn Gly Val Pro Val Phe Leu Val Asn 1415 1420 1425 Cys Ile Gln Arg Arg Thr Leu Asp Leu Leu Lys Tyr Ala Asn Phe 1430 1435 1440 Pro Leu Asp Pro Phe Leu Leu Asn Thr His Thr Asp Val Lys Asp 1445 1450 1455 Trp Leu Asp Gly Ser Arg Gly Tyr Arg Ile Gln Arg Leu Ile Glu 1460 1465 1470 Glu Leu Cys Pro Ser Glu Thr Lys Ile Met Arg Lys Leu Val Arg 1475 1480 1485 Arg Leu His His Lys Leu Lys Asn Gly Glu Cys Asn Glu Glu Phe 1490 1495 1500 Phe Leu Asp Leu Phe Asn Arg Glu Lys Lys Glu Ala Ile Leu Gln 1505 1510 1515 Leu Gly Glu Ile Leu Gly Leu Glu Asp Asp Leu Asn Glu Leu Ala 1520 1525 1530 Ser Ile Asn Trp Leu Asn Leu Asn Glu Met Phe Pro Leu Arg Met 1535 1540 1545 Val Leu Arg Gln Lys Val Val Tyr Pro Ser Val Met Thr Phe Gln 1550 1555 1560 Glu Glu Lys Ile Pro Ser Leu Ile Lys Thr Leu Gln Asn Lys Leu 1565 1570 1575 Cys Ser Lys Phe Thr Arg Gly Ala Gln Lys Leu Leu Ser Glu Ala 1580 1585 1590 Ile Asn Lys Ser Ala Phe Gln Ser Cys Val Ser Ser Gly Phe Ile 1595 1600 1605 Gly Leu Cys Lys Thr Leu Gly Ser Arg Cys Val Arg Asn Lys Asn 1610 1615 1620 Arg Glu Asn Met Tyr Ile Arg Lys Val Leu Glu Asp Leu Thr Met 1625 1630 1635 Asp Glu His Val Thr Arg Val His Lys Gln Asp Gly Val Met Leu 1640 1645 1650 Tyr Ile Cys Asp Lys Gln Arg His Pro Glu Ala His Arg Asp His 1655 1660 1665 Ile Asn Leu Leu Arg Pro Leu Leu Trp Asp Tyr Ile Cys Ile Ser 1670 1675 1680 Leu Ser Asn Ser Phe Glu Leu Gly Val Trp Val Leu Ala Glu Pro 1685 1690 1695 Val Lys Gly Lys Asn Glu Ser Asn Ser Ala Val Arg His Leu Asn 1700 1705 1710 Pro Cys Asp Tyr Val Ala Arg Lys Pro Glu Ser Ser Arg Leu Leu 1715 1720 1725 Glu Asp Lys Val Ser Leu Asn His Val Ile Gln Ser Val Arg Arg 1730 1735 1740 Leu Tyr Pro Lys Ile Phe Glu Asp Gln Leu Leu Pro Phe Met Ser 1745 1750 1755 Asp Val Ser Ser Lys Asn Met Arg Trp Ser Pro Arg Ile Lys Phe 1760 1765 1770 Leu Asp Leu Cys Val Leu Ile Asp Ile Asn Ser Glu Ser Leu Ser 1775 1780 1785 Leu Ile Ser His Val Val Lys Trp Lys Arg Asp Glu His Tyr Thr 1790 1795 1800 Val Leu Phe Ser Asp Leu Val Asn Ser His Gln Arg Ser Asp Ser 1805 1810 1815 Ser Leu Val Asp Glu Phe Val Val Ser Thr Arg Asp Val Cys Lys 1820 1825 1830 Asn Phe Leu Lys Gln Val Tyr Phe Glu Ser Phe Val Arg Glu Phe 1835 1840 1845 Val Ala Thr Ala Arg Thr Leu Gly Asn Phe Ser Trp Phe Pro His 1850 1855 1860 Lys Asp Met Met Pro Ser Glu Asp Gly Ala Glu Ala Leu Gly Pro 1865 1870 1875 Phe Gln Ser Phe Ile Leu Lys Val Val Asn Lys Lys Ile Glu Arg 1880 1885 1890 Pro Met Phe Arg Asn Asp Leu Gln Phe Gly Phe Gly Trp Phe Ser 1895 1900 1905 Tyr Arg Val Gly Asp Val Val Cys Asn Ala Ala Met Leu Ile Lys 1910 1915 1920 Gln Gly Leu Thr Asp Pro Lys Ala Phe Lys Ser Leu Arg Asp Leu 1925 1930 1935 Trp Asp Tyr Met Leu Ser Ser Thr Glu Gly Ile Leu Glu Phe Ser 1940 1945 1950 Ile Thr Val Asp Phe Thr His Asn Gln Asn Asn Thr Asp Cys Leu 1955 1960 1965 Arg Lys Phe Ser Leu Ile Phe Val Val Lys Cys Gln Leu Gln Ser 1970 1975 1980 Pro Gly Val Ala Asp Tyr Leu Ser Cys Ser His Phe Phe Lys Gly 1985 1990 1995 Glu Val Asp Arg Arg Leu Leu Asp Glu Cys Leu Asn Leu Leu Arg 2000 2005 2010 Thr Asp Pro Ile Phe Lys Ala Asn Asp Gly Val Phe Asp Ile Arg 2015 2020 2025 Ser Glu Glu Phe Glu Asp Tyr Met Glu Asp Pro Leu Thr Leu Gly 2030 2035 2040 Asp Ser Leu Glu Leu Glu Leu Ile Gly Ser Arg Arg Ile Leu Asn 2045 2050 2055 Glu Ile Lys Ser Thr Asp Phe Glu Arg Ile Gly Pro Glu Trp Glu 2060 2065 2070 Pro Val Pro Leu Thr Ile Arg Lys Gly Ala Leu Phe Glu Gly Arg 2075 2080 2085 Asn Phe Val Gln Asn Ile Ser Val Lys Leu Glu Thr Lys Asp Met 2090 2095 2100 Arg Val Phe Leu Ala Glu Leu Glu Gly Cys Gly Lys Ile Gly Asp 2105 2110 2115 Val Leu Gly Ser Leu Leu Leu His Arg Phe Arg Thr Gly Glu His 2120 2125 2130 Leu Met Glu Ser Glu Ile Ser Thr Val Leu Gln Glu Leu Cys Met 2135 2140 2145 Asp Arg Ser Val Met Leu Thr Pro Leu Ser Phe Val Pro Asp Trp 2150 2155 2160 Phe Thr Phe Arg Asp Cys Arg Leu Cys Phe Ser Arg Ser Lys Asn 2165 2170 2175 Thr Val Met Tyr Glu Thr Thr Gly Gly Arg Phe Arg Leu Lys Gly 2180 2185 2190 Lys Ser Cys Asp Asp Trp Leu Ala Glu Arg Val Ala Glu Glu Ile 2195 2200 2205 Asp <210> 17 <211> 1497 <212> DNA <213> Lymphocytic choriomeningitis virus (mutant P42) <400> 17 atgggtcaga ttgtgacaat gtttgaggct ttgcctcaca tcattgatga ggtcatcaac 60 attgtcatta ttgtgctcat tataatcacg agcatcaaag ctgtgtacaa tttcgccacc 120 tgtgggatat tagcactggt cagcttcctt tttttggctg gtaggtcctg tggcatgtac 180 ggccttaatg gtcccgacat ctataaaggg gtttaccagt tcaaatcagt ggagtttgat 240 atgtctcact taaatctgac gatgcccaat gcgtgctcag ccaacaactc tcatcactac 300 atcagtatgg gaagctctgg actggagcta actttcacta acgactccat ccttaatcac 360 aatttttgca acttaacctc cgctttcaac aaaaagactt ttgaccatac actcatgagt 420 atagtctcga gtctgcacct cagtattaga gggaattcca accacaaagc agtgtcttgt 480 gattttaaca atggcatcac cattcaatac aacttgtcat ttcggaccc acagagcgct 540 atgagccagt gtaggacttt cagaggtaga gtcttggaca tgtttagac tgcctttgga 600 ggaaaataca tgagagtgg ctggggctgg gcaggttcag atggcagac cacttggtgc 660 agccaaacaa gctatcagta cctaatcata siaaacagga cttgggaaaa ccactgtaga 720 tatgcaggcc cttttgggat gtctagaatc ctctttgctc aggaaagac aaagtttctc 780 actaggagac ttgcaggcac attcacctgg accctgtcag actcctcagg agtagaaaat 840 ccaggtggtt attgcctgac caatggatg atccttgctg cagagctca atgttttggg 900 atacagctg ttgcaaatg taatgtcaat catgatgaag agttctgtga catgctacga 960 ctaattgatt acaaaggc cgccctgagt aagttcaagc aagatgtaga gtctgccttg 1020 catgtattca aaaacagt aaattctctg atttccgatc agctgttgat gaggaatcat 1080 ctaagagatc taatgggggt accatactgt aattactcaa agttctggta tctggaacat 1140 gctaagactg gtgagactag tgtacccaag tgctggcttg tcactaatgg ctcctacttg 1200 aatgagaccc actttagtga tcaaatcgaa caagaagcag ataacatgat cacagagatg 1260 ttgaggaagg actacataaa aagacaaggg agtactcctt tagccttaat ggatcttttg 1320 atgttttcaa catcagcata tctaatcagc atctttctgc atcttgtgaa gataccaaca 1380 catagacaca taaagggcgg ttcatgtcca aagccacacc gcttgaccaa caaggggatc 1440 tgtagttgtg gtgcattcaa ggtgcctggt gtaaaaaacta tctggaaaag acgctga 1497 <210> 18 <211> 498 <212> PRT <213> Lymphoblastic plexus virus (mutant P42) <400> 18 Met Gly Gln Ile Val Thr Met Phe Glu Ala Leu Pro His Ile Ile Asp 1 5 10 15 Glu Val Ile Asn Ile Val Ile Ile Val Leu Ile Ile Thr Ser Ile 20 25 30 Lys Ala Val Tyr Asn Phe Ala Thr Cys Gly Ile Leu Ala Leu Val Ser 35 40 45 Phe Leu Phe Leu Ala Gly Arg Ser Cys Gly Met Tyr Gly Leu Asn Gly 50 55 60 Pro Asp Ile Tyr Lys Gly Val Tyr Gln Phe Lys Ser Val Glu Phe Asp 65 70 75 80 Met Ser His Leu Asn Leu Thr Met Pro Asn Ala Cys Ser Ala Asn Asn 85 90 95 Ser His His Tyr Ile Ser Met Gly Ser Ser Gly Leu Glu Leu Thr Phe 100 105 110 Thr Asn Asp Ser Ile Leu Asn His Asn Phe Cys Asn Leu Thr Ser Ala 115 120 125 Phe Asn Lys Lys Thr Phe Asp His Thr Leu Met Ser Ile Val Ser Ser 130 135 140 Leu His Leu Ser Ile Arg Gly Asn Ser Asn His Lys Ala Val Ser Cys 145 150 155 160 Asp Phe Asn Asn Gly Ile Thr Ile Gln Tyr Asn Leu Ser Phe Ser Asp 165 170 175 Pro Gln Ser Ala Met Ser Gln Cys Arg Thr Phe Arg Gly Arg Val Leu 180 185 190 Asp Met Phe Arg Thr Ala Phe Gly Gly Lys Tyr Met Arg Ser Gly Trp 195 200 205 Gly Trp Ala Gly Ser Asp Gly Lys Thr Thr Trp Cys Ser Gln Thr Ser 210 215 220 Tyr Gln Tyr Leu Ile Ile Gln Asn Arg Thr Trp Glu Asn His Cys Arg 225 230 235 240 Tyr Ala Gly Pro Phe Gly Met Ser Arg Ile Leu Phe Ala Gln Glu Lys 245 250 255 Thr Lys Phe Leu Thr Arg Arg Leu Ala Gly Thr Phe Thr Trp Thr Leu 260 265 270 Ser Asp Ser Ser Gly Val Glu Asn Pro Gly Gly Tyr Cys Leu Thr Lys 275 280 285 Trp Met Ile Leu Ala Ala Glu Leu Lys Cys Phe Gly Asn Thr Ala Val 290 295 300 Ala Lys Cys Asn Val Asn His Asp Glu Glu Phe Cys Asp Met Leu Arg 305 310 315 320 Leu Ile Asp Tyr Asn Lys Ala Ala Leu Ser Lys Phe Lys Gln Asp Val 325 330 335 Glu Ser Ala Leu His Val Phe Lys Thr Thr Val Asn Ser Leu Ile Ser 340 345 350 Asp Gln Leu Leu Met Arg Asn His Leu Arg Asp Leu Met Gly Val Pro 355 360 365 Tyr Cys Asn Tyr Ser Lys Phe Trp Tyr Leu Glu His Ala Lys Thr Gly 370 375 380 Glu Thr Ser Val Pro Lys Cys Trp Leu Val Thr Asn Gly Ser Tyr Leu 385 390 395 400 Asn Glu Thr His Phe Ser Asp Gln Ile Glu Gln Glu Ala Asp Asn Met 405 410 415 Ile Thr Glu Met Leu Arg Lys Asp Tyr Ile Lys Arg Gln Gly Ser Thr 420 425 430 Pro Leu Ala Leu Met Asp Leu Leu Met Phe Ser Thr Ser Ala Tyr Leu 435 440 445 Ile Ser Ile Phe Leu His Leu Val Lys Ile Pro Thr His Arg His Ile 450 455 460 Lys Gly Gly Ser Cys Pro Lys Pro His Arg Leu Thr Asn Lys Gly Ile 465 470 475 480 Cys Ser Cys Gly Ala Phe Lys Val Pro Gly Val Lys Thr Ile Trp Lys 485 490 495 Arg Arg <210> 19 <211> 1677 <212> DNA <213> Lymphocytic choriomeningitis virus (mutant P42) <400> 19 atgtctttgt ccaaagaagt caaaagcttt cagtggacac aggcgttgag gagggagttg 60 cagagtttta catcagatgt aaaggctgcc gtcatcaagg acgcaaccag tcttctaaat 120 gggttggact tttctgaagt cagcaacgtt cagaggatca tgagaaagga aaggggat 180 gataaagact tgcagagact caggagtctt aaccagactg tgcattctct tgttgatctg 240 aagtctacat caaagaaaaa tgttctgaaa gtgggaagac ttagtgcaga ggaattgatg 300 acccttgcag ctgatcttga gaagctgaag gccaaaatta tgagaactga gaggcctcaa 360 gcttctggag tctacatggg aaatttgaca gcacaacaac ttgatcaaag atcccaaata 420 ctgcaaatgg ttgggatgag aagacctcag cagggtgcaa gtggtgtagt aagggtttgg 480 gatgtgaagg actcatcact tctgaacaat cagttcggca caatgccaag cctgacaatg 540 gcttgcatgg caaaacagtc acagacccca ctcaatgatg ttgtgcaggc actcacagac 600 cttggcttac tttacacagt caaatacccg aatctcagtg atcttgaaag gctaaaggat 660 aaaaccccag ttctggggt cattactgaa cagcaatcta gtatcaatat ctctggttat 720 aatttcagtc ttggtgcagc tgtgaaagcg ggggcagctc tgctagatgg agggaacatg 780 ctggaatcta tcttgatcaa accgagcaac agtgaggatc tcctaaaagc agtcctcggg 840 gccaagaaga aactcaacat gtttgtctca gatcaagttg gagatagaaa tccctatgaa 900 aacatccttt ataaagtctg tcttcaggt gaaggatggc catacatagc ctgtagaacg 960 tcagttgtgg ggagagcatg ggagacaca acaatgatc tcacaatga aaacttgtt 1020 gccaactcat ctaggccagt gcctggagca gcaggccac ctcaggtggg cttgagttac 1080 agtcagacaa tgctgttgaa agacttg ggaggttg atcccaatgc tcccacatgg 1140 attgacattg agggcaggtt caatgatcca gtggagatag caatattcca accacaaat 1200 gggcaattca tacatttta caggacct aggaccaga agcaatca gcaggactca 1260 aagtattcac acggcatgga tctgctgat ctctcaatg cacagcctgg gctgacctca 1320 tcagttatag gtgctctccc acagggatg gtttgagct gtcaggttc tgatgacatc 1380 agaaagcttc tggactcaca aaatagaagg gataaaac tcattgatgt tgagatgacc 1440 aaggaggcct caagagaata tgaagaataa gtgtgggaca atatggctg gctatgcaaa 1500 atgcacactg gggtagtgag agacaaaag aagaaagaga tcacccaca ctgtgcactc 1560 atggactgca tcatttttga gagtgcttcc aaggcaagac tccctgatct aaaaaccgtt 1620 cacaacatcc tgccacatga tttaatcttc agaggaccca atgttgtgac actctaa 1677 <210> 20 <211> 558 <212> PRT <213> Lymphocytic choriomeningitis virus (mutant P42) <400> 20 Met Ser Leu Ser Lys Glu Val Lys Ser Phe Gln Trp Thr Gln Ala Leu 1 5 10 15 Arg Arg Glu Leu Gln Ser Phe Thr Ser Asp Val Lys Ala Ala Val Ile 20 25 30 Lys Asp Ala Thr Ser Leu Leu Asn Gly Leu Asp Phe Ser Glu Val Ser 35 40 45 Asn Val Gln Arg Ile Met Arg Lys Glu Arg Arg Asp Asp Lys Asp Leu 50 55 60 Gln Arg Leu Arg Ser Leu Asn Gln Thr Val His Ser Leu Val Asp Leu 65 70 75 80 Lys Ser Thr Ser Lys Lys Asn Val Leu Lys Val Gly Arg Leu Ser Ala 85 90 95 Glu Glu Leu Met Thr Leu Ala Ala Asp Leu Glu Lys Leu Lys Ala Lys 100 105 110 Ile Met Arg Thr Glu Arg Pro Gln Ala Ser Gly Val Tyr Met Gly Asn 115 120 125 Leu Thr Ala Gln Gln Leu Asp Gln Arg Ser Gln Ile Leu Gln Met Val 130 135 140 Gly Met Arg Arg Pro Gln Gln Gly Ala Ser Gly Val Val Arg Val Trp 145 150 155 160 Asp Val Lys Asp Ser Ser Leu Leu Asn Asn Gln Phe Gly Thr Met Pro 165 170 175 Ser Leu Thr Met Ala Cys Met Ala Lys Gln Ser Gln Thr Pro Leu Asn 180 185 190 Asp Val Val Gln Ala Leu Thr Asp Leu Gly Leu Leu Tyr Thr Val Lys 195 200 205 Tyr Pro Asn Leu Ser Asp Leu Glu Arg Leu Lys Asp Lys His Pro Val 210 215 220 Leu Gly Val Ile Thr Glu Gln Gln Ser Ser Ile Asn Ile Ser Gly Tyr 225 230 235 240 Asn Phe Ser Leu Gly Ala Ala Val Lys Ala Gly Ala Ala Leu Leu Asp 245 250 255 Gly Gly Asn Met Leu Glu Ser Ile Leu Ile Lys Pro Ser Asn Ser Glu 260 265 270 Asp Leu Leu Lys Ala Val Leu Gly Ala Lys Lys Lys Leu Asn Met Phe 275 280 285 Val Ser Asp Gln Val Gly Asp Arg Asn Pro Tyr Glu Asn Ile Leu Tyr 290 295 300 Lys Val Cys Leu Ser Gly Glu Gly Trp Pro Tyr Ile Ala Cys Arg Thr 305 310 315 320 Ser Val Val Gly Arg Ala Trp Glu Asn Thr Thr Ile Asp Leu Thr Asn 325 330 335 Glu Lys Leu Val Ala Asn Ser Ser Arg Pro Val Pro Gly Ala Ala Gly 340 345 350 Pro Pro Gln Val Gly Leu Ser Tyr Ser Gln Thr Met Leu Leu Lys Asp 355 360 365 Leu Met Gly Gly Ile Asp Pro Asn Ala Pro Thr Trp Ile Asp Ile Glu 370 375 380 Gly Arg Phe Asn Asp Pro Val Glu Ile Ala Ile Phe Gln Pro Gln Asn 385 390 395 400 Gly Gln Phe Ile His Phe Tyr Arg Glu Pro Thr Asp Gln Lys Gln Phe 405 410 415 Lys Gln Asp Ser Lys Tyr Ser His Gly Met Asp Leu Ala Asp Leu Phe 420 425 430 Asn Ala Gln Pro Gly Leu Thr Ser Ser Ser Val Ile Gly Ala Leu Pro Gln 435 440 445 Gly Met Val Leu Ser Cys Gln Gly Ser Asp Asp Ile Arg Lys Leu Leu 450 455 460 Asp Ser Gln Asn Arg Arg Asp Ile Lys Leu Ile Asp Val Glu Met Thr 465 470 475 480 Lys Glu Ala Ser Arg Glu Tyr Glu Asp Lys Val Trp Asp Lys Tyr Gly 485 490 495 Trp Leu Cys Lys Met His Thr Gly Val Val Arg Asp Lys Lys Lys Lys 500 505 510 Glu Ile Thr Pro His Cys Ala Leu Met Asp Cys Ile Ile Phe Glu Ser 515 520 525 Ala Ser Lys Ala Arg Leu Pro Asp Leu Lys Thr Val His Asn Ile Leu 530 535 540 Pro His Asp Leu Ile Phe Arg Gly Pro Asn Val Val Thr Leu 545 550 555 <210> twenty one <211> 273 <212> DNA <213> Lymphocytic choriomeningitis virus (mutant P42) <400> twenty one atgggccaag gcaagtccaa agaagaaagg gacaccagca atacaggcag agcagagctt 60 ttgccagaca ccacctatct tggtcctcta aattgtaaat catgttggca gaaatttgac 120 agcttggtta gatgccatga ccactatctt tgcagacact gtctgaatct cctgctgtca 180 gtttccgaca gatgtcctct ctgtaagtat ccactgccaa ccaaactgaa ggtgtcaaca 240 gtcccaagct ccccacctcc ctatgaggag tga 273 <210> twenty two <211> 90 <212> PRT <213> Lymphocytic choriomeningitis virus (mutant P42) <400> twenty two Met Gly Gln Gly Lys Ser Lys Glu Glu Arg Asp Thr Ser Asn Thr Gly 1 5 10 15 Arg Ala Glu Leu Leu Pro Asp Thr Thr Tyr Leu Gly Pro Leu Asn Cys 20 25 30 Lys Ser Cys Trp Gln Lys Phe Asp Ser Leu Val Arg Cys His Asp His 35 40 45 Tyr Leu Cys Arg His Cys Leu Asn Leu Leu Leu Ser Val Ser Asp Arg 50 55 60 Cys Pro Leu Cys Lys Tyr Pro Leu Pro Thr Lys Leu Lys Val Ser Thr 65 70 75 80 Val Pro Ser Ser Pro Pro Pro Tyr Glu Glu 85 90 <210> 23 <211> 6630 <212> DNA <213> Lymphocytic choriomeningitis virus (mutant P42) <400> 23 atggatgaaa ctattgcaga tttgagagag ttgtgtctaa attacataga acaggacgag 60 aggctgtcaa ggcaaaaact caacttcctg ggacaaagag aacccagaat ggtgctaatt 120 gagggactca aattgttatc acgctgtata gagatagaca gtgcagacaa aagtggttgc 180 atacacaacc acgatgacaa atctgttgaa acaatcctaa tagactctgg gattgtgtgt 240 ccaggactgc cactcatcat ccctgatggt tataagttga ttgacaattc ccttattctt 300 cttgaatgtt ttgttagaag cacaccagct agttttgaaa agaagttcat tgaggacacc 360 aacaaactag catgcatcaa agaagatctt gctgttgcag gcatcacact ggttccaata 420 gtggatggtc gttgtgatta tgataacagt ttcatgccag aatgggtgaa ttttaagttc 480 agagacctcc tatttaaact cctggagtat tctagtcaag atgagaaagt ttttgaggag 540 tctgaatact tcaggctctg tgagtctctt aagaccactg ttgacaaacg ttccggcatg 600 gactcaatga aaattttgaa agacgcaaga tcatttcata acgatgagat tatgaaaatg 660 tgccacgatg gtgtcaaccc caacatgagt tgcgatgatg tggtctttgg cataaattcc 720 tttttggca ggtttaggag ggacctgtta aatgggaaac tcaaaaggaa tttccaaaag 780 gtcagccctg ggggcttaat caaggaattc tctgaacttt atgaaaccct tactgataat 840 gatgacatat taatgttgag caaagaggca gttgaatcct gccccttaat gaggttcatt 900 960 ctctctatgt tgaacaaggt gaaaagttta aaattattaa acactagaag gagacagctg 1020 ctgaacttag atgtcttatg tctttcttca cttattaagc agtcaatttc caaagggttg 1080 gaaaatgata aacattgggt tggttgttgc tacagtagtg tgaatgatag gcttgtgagc 1140 cttcaaagta ccaaagaaga attcatgaga cttttgaaga acagaagaaa atcaagagtg 1200 cacaaaaagg catctcttga tgagcttttt agggtatcca taaatgagtt catagcaaaa 1260 atccagaaat gcctatcaac agtgggactt agttttgagc attacggact atcagaatgc 1320 ctcgtgcaag aatgccatat accatttgct gaatttgaga actttatgag agccgggact 1380 catcctgtaa tgcattacac aaaatttgaa gattacactt tccagcctaa catagagcaa 1440 ttgaggggtt tacagagttt gagaaaactg tcatctgttt gtttggctct aacaaacagc 1500 atgaaaacaa gctcagttgc aaggttgaga cagaaccaac tggggtctgt gagatatcaa 1560 gtggtggagt gcaaagaggt gttttgccag ataataaaac tggattccga agagtatcat 1620 ctactatatc agaaaactgg agaatcatcg aggtgttatt ccatacaagg tccggatggt 1680 cacttgattt ccttttacgc agatccaaaa aggttctttt taccaattttt ttcagatgag 1740 gtgttgcaca acatgataga cacaatgatt tcatggatta ggtcatgccc tgacttaaaa 1800 gattctctta ttgacattga gactgcacta aggacattga tcctactgat gctcaccaac 1860 ccaacaaaga gaaatcaaaa gcaggttcaa aatattaggt atttagtgat ggccatcgtc 1920 tcagacttt catcgacctc attaatggat aagttgaagg aggatctaat cacacctgcc 1980 gagaaagtgg tgtacaggct gcttcggttt ttgattagga caatttttgg tactggtgaa 2040 aaggtgttat tgagtgcaaa attcaagttt atgttgaatg tgtcatacct gtgtcatttg 2100 atcacaaagg agacccctga tagattgaca gatcagataa aatgttttga aaagttcttt 2160 gagcccaaga gtgagtttgg tttctttgtc aaccctaagg aaacaatcac acccgaagag 2220 gaatgtgttt tttatgaaca aatgaagaag ttcaccggta aagatattga ttgtcagcat 2280 tcaacccctg gtgttaattt agagatcttt agcatgatgg tatcttcatt caacaatggc 2340 accttaattc taaaagggga gaaaaggctc aacaatctgg accccacatgac caactctgga 2400 tgtgcgacag cattagatct cgcaagcaac aaaagtgtgg ttgtcaataa acatctgaat 2460 ggagaacggc ttttggagta tgattttaac aaattgcttg ttagtgctgt gagccaaatt 2520 acagagggct tcatgaggaa acaaaagtat aagctgagac actcagatta cgaatataag 2580 gtctcaaagc ttgtctctag attagtcatc ggttccagga aaacagaagt agacaaattg 2640 gaagatgatc cggtagatgt gtgtttcgag ggggaggagg agacaagttt tttcaggagt 2700 ttagaagata aggtcagctc cacaataaca cggtataata gaggcactag gcttaatgaa 2760 gggcaagggg agggagaatt caagaacaca aaaggactac accaccttca gattattttg 2820 tcaggtaaaa gagcttatct gaggaaagtc attttatcag aaatttcatt tcatctagta 2880 gaggactttg atccatcctg tctcaccaat gacgacatga ggtttatttg tgaggctgtt 2940 gaaggttcaa cagaactgtc accattgtat tttacatcag ctgtcaaaga acaatgtggt 3000 ctggatgaga tggcaagaaa cctctgtaga aagttcttct cagagggtga ttggttctca 3060 tgtatgaaga tgatcttgtt acagatgaat gcaaatgcgt attcagggaa gtacagacac 3120 atgcagaggc agagcttaaa ttttaaattt gactgggaca aattggaaga agatgtaaga 3180 attagtgaaa gggaaagcaa ttctgaatct ctaagtaagg ccctttcatt gacaaaatgc 3240 atgagtgctg ctctaaagaa tctgtgtttt tactcagaag aatcaccaac atcatacact 3300 tcagttggcc ctgactctgg gagactaaaa tttgcattgt catacaaaga gcaggttggg 3360 ggaatagag agctttacat tggggatttg aggacaaaaa tgttcacaag attggtagaa 3420 gattattttg aatccttttc tagtttcttt tcaggatctt gtttaaacaa tgacaaagag 3480 tttgaaaatg caatcttgtc aatgactatc aatgtgagag aagggttgtt aaactacagc 3540 atggatcaca gcaaatgggg accaatgatg tgcccattcc tattcttaat gctyctccaa 3600 aatctcaaac tgggtgatga tcagtacgtg cgttctggaa aagatcatgt tagcaccttg 3660 ttgacttggc atatgcataa acttgttgaa gtccctttcc ctgttgtgaa tgcaatgatg 3720 aaatcatatg ttaaatcaaa actcaagctt ctcaaagggt caggaacgac tgttacggag 3780 agaatcttta gagagtattt tgaaatgggg gtggtgccat ctcacatatc tagtctcatt 3840 gacatgggac aggggatcct acacaatgct tctgattttt acggtttaat tagtgaaagg 3900 tttatcaatt attgtattgg tgtcattttt ggagagaggc cagaagccta tacatcaagt 3960 gatgatcaga tcactttatt tgacaagaga ttgagtgact tagttgatag tgacccagaa 4020 gaagtccttg tcttgctgga attccactct cacttaagtg gtttgttgaa caagttcatc 4080 agtccaaaaa gtgtggttgg gcggtttgca gcggaattca aatccagatt ttatgtgtgg 4140 ggggaggagg tccctctcct cacgaaattt gtgtctgcgg cactacacaa tgttaagtgt 4200 aaagaaccgc atcaactttg tgagacaata gatacgattg ctgatcaagc tatagcaaat 4260 ggagttccag ttttttagt aaactgtatc cagaggagga cactggatct cttgaaatat 4320 gctaatttcc ctttagatcc attcttgtta aacactcaca ctgatgtaaa ggattggtta 4380 gatggttcta gaggttatag aatccaaaga ctcattgaag aattgtgtcc cagtgaaaca 4440 aagatcatga gaaaacttgt aagaagacta catcacaaac tcaagaacgg tgaatgtaac 4500 gaggaattt ttctagacct cttcaacagg gaaaagaaag aggccatcct tcaattggga 4560 gagattcttg gtcttgagga tgatcttaat gagttggcaa gcatcaattg gttgaatctg 4620 aatgaaatgt tcccattgag gatggttctg agacaaaaag tggtttaccc atcagtratg 4680 acctttcaag aggaaaagat cccctcattg attaaaacac tccaaaataa gctttgtagt 4740 aagttcacaa gaggtgcaca gaagctgttg tcagaggcaa tcaacaaatc agcttttcag 4800 agttgtgtct catccggctt tataggtctc tgtaagactt taggaagtag gtgtgtgaga 4860 aataaaaaca gggaaaatat gtatatcaga aaggtgcttg aagatctgac catggatgaa 4920 catgtcacaa gggttcacaa acaagatggt gtgatgttgt acatttgcga caagcagaga 4980 cacccagagg ctcaccgtga ccacatcaac cttttgaggc cccttctctg ggactacatt 5040 tgcatctcat tgagcaactc ttttgagctg ggtgtttggg ttttagcaga acctgtgaaa 5100 ggaaagaacg agagtaattc ggctgttagg cacttaaatc catgtgatta tgtagcaaga 5160 aaacctgaga gttcgagact actagaggat aaagtgagtt tgaatcatgt aattcaatct 5220 gtgaggcgac tgtaccccaa aatctttgag gatcagttgc tcccattcat gtttgatgtg 5280 agctcaaaaa atatgagatg gagtcccagg attaaattcc ttgacctttg tgtgctgatt 5340 gacatcaact cagagtcttt gtcactcatt tctcatgttg tcaaatggaa gagggacgaa 5400 cattacactg tgctgttttc tgatctcgtc aactctcacc aacggtcaga ctcaagttta 5460 gttgatgaat ttgttgtcag cacaagggat gtctgcaaga actttttgaa gcaagtgtat 5520 ttcgaatcat ttgtacgaga gtttgttgca acagctagga ccttaggtaa cttttcatgg 5580 ttcccccata aggacatgat gccatctgaa gatggcgctg aagcactggg acccttccaa 5640 tcatttatt tgaaagtggt gaacaagaaa atagagaggc ccatgtttag gaatgacttg 5700 cagtttggtt ttggttggtt ccttatcgt gtgggggatg ttgtgtgtaa tgccgctatg 5760 ttaattaagc agggtttgac agatccaaaa gcatttaaat ctttaagaga tttgtgggat 5820 tacatgctca gcagcacaga ggggatattg gagttctcaa tcacagtgga tttcacacac 5880 aaccagaaca acactgactg cttgaggaaa ttttcattga tctttgtggt taaatgccaa 5940 ttacagagtc caggtgtagc tgattactta tcgtgctctc atttcttcaa aggtgaggtt 6000 gacaggagat tattagatga gtgtctcaat ctgttgagga cagaccccat cttaaagcg 6060 aatgatggag tctttgacat taggtctgaa gagtttgaag attacatgga agaccctttg 6120 acacttggtg attcactaga acttgaacta ataggttcta gaaggattct gaatgagatc 6180 aaatctactg actttgagag gatagggcct gagtgggaac ctgtgcctct gaccataagg 6240 aagggtgccc tctttgaggg gaggaacttt gttcagaata tctctgtgaa attggagaca 6300 aaggacatga grgtctttct ggcagagctc gagggctgtg gaaaaattgg tgatgtcctc 6360 ggcagcctcc tcctgcaccg attcagaact ggtgagcact tgatggagtc agaaataagt 6420 acagttcttc aggagctctg catggacaga tccgtcatgc tgacaccatt atcttttgtg 6480 ccagattggt tcaccttcag agattgtagg ctctgcttca gcaggtcaaa gaacactgtr 6540 atgtatgaga caactggggg caggttcaga ctcaagggga aatcctgtga cgattggctg 6600 gcggagcggg tggccgagga gatcgactag 6630 <210> twenty four <211> 2209 <212> PRT <213> Lymphocytic choriomeningitis virus (mutant P42) <400> twenty four Met Asp Glu Thr Ile Ala Asp Leu Arg Glu Leu Cys Leu Asn Tyr Ile 1 5 10 15 Glu Gln Asp Glu Arg Leu Ser Arg Gln Lys Leu Asn Phe Leu Gly Gln 20 25 30 Arg Glu Pro Arg Met Val Leu Ile Glu Gly Leu Lys Leu Leu Ser Arg 35 40 45 Cys Ile Glu Ile Asp Ser Ala Asp Lys Ser Gly Cys Ile His Asn His 50 55 60 Asp Asp Lys Ser Val Glu Thr Ile Leu Ile Asp Ser Gly Ile Val Cys 65 70 75 80 Pro Gly Leu Pro Leu Ile Ile Pro Asp Gly Tyr Lys Leu Ile Asp Asn 85 90 95 Ser Leu Ile Leu Leu Glu Cys Phe Val Arg Ser Thr Pro Ala Ser Phe 100 105 110 Glu Lys Lys Phe Ile Glu Asp Thr Asn Lys Leu Ala Cys Ile Lys Glu 115 120 125 Asp Leu Ala Val Ala Gly Ile Thr Leu Val Pro Ile Val Asp Gly Arg 130 135 140 Cys Asp Tyr Asp Asn Ser Phe Met Pro Glu Trp Val Asn Phe Lys Phe 145 150 155 160 Arg Asp Leu Leu Phe Lys Leu Leu Glu Tyr Ser Ser Gln Asp Glu Lys 165 170 175 Val Phe Glu Glu Ser Glu Tyr Phe Arg Leu Cys Glu Ser Leu Lys Thr 180 185 190 Thr Val Asp Lys Arg Ser Gly Met Asp Ser Met Lys Ile Leu Lys Asp 195 200 205 Ala Arg Ser Phe His Asn Asp Glu Ile Met Lys Met Cys His Asp Gly 210 215 220 Val Asn Pro Asn Met Ser Cys Asp Asp Val Val Phe Gly Ile Asn Ser 225 230 235 240 Phe Phe Gly Arg Phe Arg Arg Asp Leu Leu Asn Gly Lys Leu Lys Arg 245 250 255 Asn Phe Gln Lys Val Ser Pro Gly Gly Leu Ile Lys Glu Phe Ser Glu 260 265 270 Leu Tyr Glu Thr Leu Thr Asp Asn Asp Asp Ile Leu Met Leu Ser Lys 275 280 285 Glu Ala Val Glu Ser Cys Pro Leu Met Arg Phe Ile Thr Ala Glu Thr 290 295 300 His Gly His Glu Arg Gly Ser Asp Ala Asn Thr Glu Tyr Glu Arg Leu 305 310 315 320 Leu Ser Met Leu Asn Lys Val Lys Ser Leu Lys Leu Leu Asn Thr Arg 325 330 335 Arg Arg Gln Leu Leu Asn Leu Asp Val Leu Cys Leu Ser Ser Leu Ile 340 345 350 Lys Gln Ser Ile Ser Lys Gly Leu Glu Asn Asp Lys His Trp Val Gly 355 360 365 Cys Cys Tyr Ser Ser Val Asn Asp Arg Leu Val Ser Leu Gln Ser Thr 370 375 380 Lys Glu Glu Phe Met Arg Leu Leu Lys Asn Arg Arg Lys Ser Arg Val 385 390 395 400 His Lys Lys Ala Served Asp Glu To Phe Arg Val Served Ile Asn Glu 405 410 415 Phe and Ala Lys and Gln Lys Cys can be found in Thr Val Gly 420 425 430 Glu His Tyr Gly Leu Ser Glu Cys Leu Val Gln Glu Cys His Ile Pro 435 440 445 Phe Ala Glu Phe Glu Asn Phe Met Arg Ala Gly Thr His Pro Val Met 450 455 460 His Tyr Thr Lys Phe Glu Asp Tyr Thr Phe Gln Pro Asn Ile Glu Gln 465 470 475 480 Leu Arg Gly Leu Gln Ser Leu Arg Leu Ser Val Cys Leu Wing 485,490,495 Leu Thr Asn Will Be Met Lys Thr Will Be Val Ala Arg Leu Arg Gln Asn 500 505 510 Gln Leu Gly Ser Val Arg Tyr Gln Val Val Glu Cys Lys Glu Val Phe 515,520,525 Cys Gln Ile Ile Lys Leu Asp Ser Glu Glu Tyr His Leu Tyr Gln 530 535 540 Lys Thr Gly Glu Ser Ser Arg Cys Tyr Ser Ile Gln Gly Pro Asp Gly 545 550 555 560 His Leu Ile Ser Phe Tyr Ala Asp Pro Lys Arg Phe Phe Leu Pro Ile 565 570 575 Phe Ser Asp Glu Val Leu His Asn Met Ile Asp Thr Met Ile Ser Trp 580 585 590 Ile Arg Ser Cys Pro Asp Leu Lys Asp Ser Leu Ile Asp Ile Glu Thr 595 600 605 Ala Leu Arg Thr Leu Ile Leu Leu Met Leu Thr Asn Pro Thr Lys Arg 610 615 620 Asn Gln Lys Gln Val Gln Asn Ile Arg Tyr Leu Val Met Ala Ile Val 625 630 635 640 Ser Asp Phe Ser Ser Thr Ser Leu Met Asp Lys Leu Lys Glu Asp Leu 645 650 655 Ile Thr Pro Ala Glu Lys Val Val Tyr Arg Leu Leu Arg Phe Leu Ile 660 665 670 Arg Thr Ile Phe Gly Thr Gly Glu Lys Val Leu Leu Ser Ala Lys Phe 675 680 685 Lys Phe Met Leu Asn Val Ser Tyr Leu Cys His Leu Ile Thr Lys Glu 690 695 700 Thr Pro Asp Arg Leu Thr Asp Gln Ile Lys Cys Phe Glu Lys Phe Phe 705 710 715 720 Glu Pro Lys Ser Glu Phe Gly Phe Phe Val Asn Pro Lys Glu Thr Ile 725 730 735 Thr Pro Glu Glu Glu Cys Val Phe Tyr Glu Gln Met Lys Lys Phe Thr 740 745 750 Gly Lys Asp Ile Asp Cys Gln His Ser Thr Pro Gly Val Asn Leu Glu 755 760 765 Ile Phe Ser Met Met Val Ser Ser Phe Asn Asn Gly Thr Leu Ile Leu 770 775 780 Lys Gly Glu Lys Arg Leu Asn Asn Leu Asp Pro Met Thr Asn Ser Gly 785 790 795 800 Cys Ala Thr Ala Leu Asp Leu Ala Ser Asn Lys Ser Val Val Val Asn 805 810 815 Lys His Leu Asn Gly Glu Arg Leu Leu Glu Tyr Asp Phe Asn Lys Leu 820 825 830 Leu Val Ser Ala Val Ser Gln Ile Thr Glu Gly Phe Met Arg Lys Gln 835 840 845 Lys Tyr Lys Leu Arg His Ser Asp Tyr Glu Tyr Lys Val Ser Lys Leu 850 855 860 Val Ser Arg Leu Val Ile Gly Ser Arg Lys Thr Glu Val Asp Lys Leu 865 870 875 880 Glu Asp Asp Pro Val Asp Val Cys Phe Glu Gly Glu Glu Glu Thr Ser 885 890 895 Phe Phe Arg Ser Leu Glu Asp Lys Val Ser Ser Thr Ile Thr Arg Tyr 900 905 910 Asn Arg Gly Thr Arg Leu Asn Glu Gly Gln Gly Glu Gly Glu Phe Lys 915 920 925 Asn Thr Lys Gly Leu His His Leu Gln Ile Ile Leu Ser Gly Lys Arg 930 935 940 Ala Tyr Leu Arg Lys Val Ile Leu Ser Glu Ile Ser Phe His Leu Val 945 950 955 960 Glu Asp Phe Asp Pro Ser Cys Leu Thr Asn Asp Asp Met Arg Phe Ile 965 970 975 Cys Glu Ala Val Glu Gly Ser Thr Glu Leu Ser Pro Leu Tyr Phe Thr 980 985 990 Ser Ala Val Lys Glu Gln Cys Gly Leu Asp Glu Met Ala Arg Asn Leu 995 1000 1005 Cys Arg Lys Phe Phe Ser Glu Gly Asp Trp Phe Ser Cys Met Lys 1010 1015 1020 Met Ile Leu Gln With Asn Only Asn Only Tyr Ser Gly Lys Tyr 1025 1030 1035 Arg His Met Gln Arg Gln Ser Leu Asn Phe Lys Phe Asp Trp Asp 1040 1045 1050 Lys Leu Glu Glu Asp Val Arg Ile Ser Glu Arg Glu Ser Asn Ser 1055 1060 1065 Glu Ser Leu Ser Lys Ala Leu Ser Thr Lys Cys Met Ser Ala 1070 1075 1080 Ala Leu Lys Asn Leu Cys Phe Tyr Ser Glu Glu Ser Pro Thr Ser 1085 1090 1095 Tyr Thr Ser Val Gly Pro Asp Ser Gly Arg Leu Lys Phe Ala Leu 1100 1105 1110 Tyr Lys Gln Val Gly Gly Asn Arg Glu Leu Tyr Ile Gly 1115 1120 1125 Asp Leu Arg Thr Lys Met Phe Thr Arg Leu Val Glu Asp Tyr Phe 1130 1135 1140 Glu Ser PhE Ser PHE PHE Ser Gly Ser Cys Leu Asn Asn Asp 1145 1150 1155 Lys Glu Phe Glu Asn Ala Ile Leu Ser Met Thr Ile Asn Val Arg 1160 1165 1170 Glu Gly Leu Leu Asn Tyr Ser Met Asp His Ser Lys Trp Gly Pro 1175 1180 1185 Met Met Cys Pro Phe Leu Phe Leu Met Leu Leu Gln Asn Leu Lys 1190 1195 1200 Leu Gly Asp Asp Gln Tyr Val Arg Ser Gly Lys Asp His Val Ser 1205 1210 1215 Thr Leu Leu Thr Trp His Met His Lys Leu Val Glu Val Pro Phe 1220 1225 1230 Pro Val Val Asn Ala Met Met Lys Ser Tyr Val Lys Ser Lys Leu 1235 1240 1245 Lys Leu Leu Lys Gly Ser Gly Thr Thr Val Thr Glu Arg Ile Phe 1250 1255 1260 Arg Glu Tyr Phe Glu Met Gly Val Val Pro Ser His Ile Ser Ser 1265 1270 1275 Leu Ile Asp Met Gly Gln Gly Ile Leu His Asn Ala Ser Asp Phe 1280 1285 1290 Tyr Gly Leu Ile Ser Glu Arg Phe Ile Asn Tyr Cys Ile Gly Val 1295 1300 1305 Ile Phe Gly Glu Arg Pro Glu Ala Tyr Thr Ser Ser Asp Asp Gln 1310 1315 1320 Ile Thr Leu Phe Asp Lys Arg Leu Ser Asp Leu Val Asp Ser Asp 1325 1330 1335 Pro Glu Glu Val Leu Val Leu Leu Glu Phe His Ser His Leu Ser 1340 1345 1350 Gly Leu Leu Asn Lys Phe Ile Ser Pro Lys Ser Val Val Gly Arg 1355 1360 1365 Phe Ala Ala Glu Phe Lys Ser Arg Phe Tyr Val Trp Gly Glu Glu 1370 1375 1380 Val Pro Leu Leu Thr Lys Phe Val Ser Ala Ala Leu His Asn Val 1385 1390 1395 Lys Cys Lys Glu Pro His Gln Leu Cys Glu Thr Ile Asp Thr Ile 1400 1405 1410 Ala Asp Gln Ala Ile Ala Asn Gly Val Pro Val Phe Leu Val Asn 1415 1420 1425 Cys Ile Gln Arg Arg Thr Leu Asp Leu Leu Lys Tyr Ala Asn Phe 1430 1435 1440 Pro Leu Asp Pro Phe Leu Leu Asn Thr His Thr Asp Val Lys Asp 1445 1450 1455 Trp Leu Asp Gly Ser Arg Gly Tyr Arg Ile Gln Arg Leu Ile Glu 1460 1465 1470 Glu Leu Cys Pro Ser Glu Thr Lys Ile Met Arg Lys Leu Val Arg 1475 1480 1485 Arg Leu His His Lys Leu Lys Asn Gly Glu Cys Asn Glu Glu Phe 1490 1495 1500 Phe Leu Asp Leu Phe Asn Arg Glu Lys Lys Glu Ala Ile Leu Gln 1505 1510 1515 Leu Gly Glu Ile Leu Gly Leu Glu Asp Asp Leu Asn Glu Leu Ala 1520 1525 1530 Ser Ile Asn Trp Leu Asn Leu Asn Glu Met Phe Pro Leu Arg Met 1535 1540 1545 Val Leu Arg Gln Lys Val Val Tyr Pro Ser Val Met Thr Phe Gln 1550 1555 1560 Glu Glu Lys Ile Pro Ser Leu Ile Lys Thr Leu Gln Asn Lys Leu 1565 1570 1575 Cys Ser Lys Phe Thr Arg Gly Ala Gln Lys Leu Leu Ser Glu Ala 1580 1585 1590 Ile Asn Lys Ser Ala Phe Gln Ser Cys Val Ser Ser Gly Phe Ile 1595 1600 1605 Gly Leu Cys Lys Thr Leu Gly Ser Arg Cys Val Arg Asn Lys Asn 1610 1615 1620 Arg Glu Asn Met Tyr Ile Arg Lys Val Leu Glu Asp Leu Thr Met 1625 1630 1635 Asp Glu His Val Thr Arg Val His Lys Gln Asp Gly Val Met Leu 1640 1645 1650 Tyr Ile Cys Asp Lys Gln Arg His Pro Glu Ala His Arg Asp His 1655 1660 1665 Ile Asn Leu Leu Arg Pro Leu Leu Trp Asp Tyr Ile Cys Ile Ser 1670 1675 1680 Leu Ser Asn Ser Phe Glu Leu Gly Val Trp Val Leu Ala Glu Pro 1685 1690 1695 Val Lys Gly Lys Asn Glu Ser Asn Ser Ala Val Arg His Leu Asn 1700 1705 1710 Pro Cys Asp Tyr Val Ala Arg Lys Pro Glu Ser Ser Arg Leu Leu 1715 1720 1725 Glu Asp Lys Val Ser Leu Asn His Val Ile Gln Ser Val Arg Arg 1730 1735 1740 Leu Tyr Pro Lys Ile Phe Glu Asp Gln Leu Leu Pro Phe Met Phe 1745 1750 1755 Asp Val Ser Ser Lys Asn Met Arg Trp Ser Pro Arg Ile Lys Phe 1760 1765 1770 Leu Asp Leu Cys Val Leu Ile Asp Ile Asn Ser Glu Ser Leu Ser 1775 1780 1785 Leu Ile Ser His Val Val Lys Trp Lys Arg Asp Glu His Tyr Thr 1790 1795 1800 Val Leu Phe Ser Asp Leu Val Asn Ser His Gln Arg Ser Asp Ser 1805 1810 1815 Ser Leu Val Asp Glu Phe Val Val Ser Thr Arg Asp Val Cys Lys 1820 1825 1830 Asn Phe Leu Lys Gln Val Tyr Phe Glu Ser Phe Val Arg Glu Phe 1835 1840 1845 Val Ala Thr Ala Arg Thr Leu Gly Asn Phe Ser Trp Phe Pro His 1850 1855 1860 Lys Asp Met Met Pro Ser Glu Asp Gly Ala Glu Ala Leu Gly Pro 1865 1870 1875 Phe Gln Ser Phe Ile Leu Lys Val Val Asn Lys Lys Ile Glu Arg 1880 1885 1890 Pro Met Phe Arg Asn Asp Leu Gln Phe Gly Phe Gly Trp Phe Ser 1895 1900 1905 Tyr Arg Val Gly Asp Val Val Cys Asn Ala Ala Met Leu Ile Lys 1910 1915 1920 Gln Gly Leu Thr Asp Pro Lys Ala Phe Lys Ser Leu Arg Asp Leu 1925 1930 1935 Trp Asp Tyr Met Leu Ser Ser Thr Glu Gly Ile Leu Glu Phe Ser 1940 1945 1950 Ile Thr Val Asp Phe Thr His Asn Gln Asn Asn Thr Asp Cys Leu 1955 1960 1965 Arg Lys Phe Ser Leu Ile Phe Val Val Lys Cys Gln Leu Gln Ser 1970 1975 1980 Pro Gly Val Ala Asp Tyr Leu Ser Cys Ser His Phe Phe Lys Gly 1985 1990 1995 Glu Val Asp Arg Arg Leu Leu Asp Glu Cys Leu Asn Leu Leu Arg 2000 2005 2010 Thr Asp Pro Ile Phe Lys Ala Asn Asp Gly Val Phe Asp Ile Arg 2015 2020 2025 Ser Glu Glu Phe Glu Asp Tyr Met Glu Asp Pro Leu Thr Leu Gly 2030 2035 2040 Asp Ser Leu Glu Leu Glu Leu Ile Gly Ser Arg Arg Ile Leu Asn 2045 2050 2055 Glu Ile Lys Ser Thr Asp Phe Glu Arg Ile Gly Pro Glu Trp Glu 2060 2065 2070 Pro Val Pro Leu Thr Ile Arg Lys Gly Ala Leu Phe Glu Gly Arg 2075 2080 2085 Asn Phe Val Gln Asn Ile Ser Val Lys Leu Glu Thr Lys Asp Met 2090 2095 2100 Arg Val Phe Leu Ala Glu Leu Glu Gly Cys Gly Lys Ile Gly Asp 2105 2110 2115 Val Leu Gly Ser Leu Leu Leu His Arg Phe Arg Thr Gly Glu His 2120 2125 2130 Leu Met Glu Ser Glu Ile Ser Thr Val Leu Gln Glu Leu Cys Met 2135 2140 2145 Asp Arg Ser Val Met Leu Thr Pro Leu Ser Phe Val Pro Asp Trp 2150 2155 2160 Phe Thr Phe Arg Asp Cys Arg Leu Cys Phe Ser Arg Ser Lys Asn 2165 2170 2175 Thr Val Met Tyr Glu Thr Thr Gly Gly Arg Phe Arg Leu Lys Gly 2180 2185 2190 Lys Ser Cys Asp Asp Trp Leu Ala Glu Arg Val Ala Glu Glu Ile 2195 2200 2205 Asp <210> 25 <211> 1497 <212> DNA <213> Lymphocytic choriomeningitis virus (mutant P52) <400> 25 atgggtcaga ttgtgacaat gtttgaggct ttgcctcaca tcattgatga ggtcatcaac 60 attgtcatta ttgtgctcat tataatcacg agcatcaaag ctgtgtacaa tttcgccacc 120 tgtgggatat tagcactggt cagcttcctt tttttggctg gtaggtcctg tggcatgtac 180 ggccttaatg gtcccgacat ctataaaggg gtttaccagt tcaaatcagt ggagtttgat 240 atgtctcact taaatctgac gatgcccaat gcgtgctcag ccaacaactc tcatcactac 300 atcagtatgg gaagctctgg actggagcta actttcacta acgactccat ccttaatcac 360 aatttttgca acttaacctc cgctttcaac aaaaagactt ttgaccatac actcatgagt 420 atagtctcga gtctgcacct cagtattaga gggaattcca accacaaagc agtgtcttgt 480 gattttaaca atggcatcac cattcaatac aacttgtcat tttcggaccc acagagcgct 540 atgagccagt gttggacttt cagaggtaga gtcttggaca tgtttagaac tgcctttgga 600 ggaaaataca tgagagtgg ctggggctgg gcaggttcag atggcagac cacttggtgc 660 agccaaacaa gctatcagta cctaatcata siaaacagga cttgggaaaa ccactgtaga 720 tatgcaggcc cttttgggat gtctagaatc ctctttgctc aggaaagac aaagtttctc 780 actaggagac ttgcaggcac attcacctgg accctgtcag actcctcagg agtagaaaat 840 ccaggtggtt attgcctgac caatggatg atccttgctg cagagctca atgttttggg 900 atacagctg ttgcaaatg taatgtcaat catgatgaag agttctgtga catgctacga 960 ctaattgatt acaaaggc cgccctgagt aagttcaagc aagatgtaga gtctgccttg 1020 catgtattca aaaacagt aaattctctg atttccgatc agctgttgat gaggaatcat 1080 ctaagagatc taatgggggt accatactgt aattactcaa agttctggta tctggaacat 1140 gctaagactg gtgagactag tgtacccaag tgctggcttg tcactaatgg ctcctacttg 1200 aatgagaccc actttagtga tcaatcgaaaaccag atacatgat acttagtg 1260 ttgaggagg actacataaa aagacaaggg agtactcctt tagccttaat ggatctttg 1320 atgttttcaa catcagcata tctaatcagc atctttctgc atcttgtgaa gataccaaca 1380 catagacaca taaagggcgg ttcatgtcca aagccacaccc gcttgaccaa caaggggatc 1440 tgtagttgtg gtgcattcaa ggtgcctggt gtaaaaacta tctggaaaag acgctga 1497 <210> 26 <211> 498 <212> PRT <213> Lymphocytic choriomeningitis virus (mutant P52) <400> 26 Met Gly Gln Ile Val Thr Met Phe Glu Ala Leu Pro His Ile Ile Asp 1 5 10 15 Glu Val Ile Asn Ile Val Ile Ile Val Leu Ile Ile Ile Thr Ser Ile 20 25 30 Lys Ala Val Tyr Asn Phe Ala Thr Cys Gly Ile Leu Ala Leu Val Ser 35 40 45 Phe Leu Phe Leu Ala Gly Arg Ser Cys Gly Met Tyr Gly Leu Asn Gly 50 55 60 Pro Asp Ile Tyr Lys Gly Val Tyr Gln Phe Lys Ser Val Glu Phe Asp 65 70 75 80 Met Ser His Leu Asn Leu Thr Met Pro Asn Ala Cys Ser Ala Asn Asn 85 90 95 Ser His His Tyr Ile Ser Met Gly Ser Ser Gly Leu Glu Leu Thr Phe 100 105 110 Thr Asn Asp Ser Ile Leu Asn His Asn Phe Cys Asn Leu Thr Ser Ala 115 120 125 Phe Asn Lys Lys Thr Phe Asp His Thr Leu Met Ser Ile Val Ser Ser 130 135 140 Leu His Leu Ser Ile Arg Gly Asn Ser Asn His Lys Ala Val Ser Cys 145 150 155 160 Asp Phe Asn Asn Gly Ile Thr Ile Gln Tyr Asn Leu Ser Phe Ser Asp 165 170 175 Pro Gln Ser Ala Met Ser Gln Cys Trp Thr Phe Arg Gly Arg Val Leu 180 185 190 Asp Met Phe Arg Thr Ala Phe Gly Gly Lys Tyr Met Arg Ser Gly Trp 195 200 205 Gly Trp Ala Gly Ser Asp Gly Lys Thr Thr Trp Cys Ser Gln Thr Ser 210 215 220 Tyr Gln Tyr Leu Ile Ile Gln Asn Arg Thr Trp Glu Asn His Cys Arg 225 230 235 240 Tyr Ala Gly Pro Phe Gly Met Ser Arg Ile Leu Phe Ala Gln Glu Lys 245 250 255 Thr Lys Phe Leu Thr Arg Arg Leu Ala Gly Thr Phe Thr Trp Thr Leu 260 265 270 Ser Asp Ser Ser Gly Val Glu Asn Pro Gly Gly Tyr Cys Leu Thr Lys 275 280 285 Trp Met Ile Leu Ala Ala Glu Leu Lys Cys Phe Gly Asn Thr Ala Val 290 295 300 Ala Lys Cys Asn Val Asn His Asp Glu Glu Phe Cys Asp Met Leu Arg 305 310 315 320 Leu Ile Asp Tyr Asn Lys Ala Ala Leu Ser Lys Phe Lys Gln Asp Val 325 330 335 Glu Ser Ala Leu His Val Phe Lys Thr Thr Val Asn Ser Leu Ile Ser 340 345 350 Asp Gln Leu Leu Met Arg Asn His Leu Arg Asp Leu Met Gly Val Pro 355 360 365 Tyr Cys Asn Tyr Ser Lys Phe Trp Tyr Leu Glu His Ala Lys Thr Gly 370 375 380 Glu Thr Ser Val Pro Lys Cys Trp Leu Val Thr Asn Gly Ser Tyr Leu 385 390 395 400 Asn Glu Thr His Phe Ser Asp Gln Ile Glu Gln Glu Ala Asp Asn Met 405 410 415 Ile Thr Glu Met Leu Arg Lys Asp Tyr Ile Lys Arg Gln Gly Ser Thr 420 425 430 Pro Leu Ala Leu Met Asp Leu Leu Met Phe Ser Thr Ser Ala Tyr Leu 435 440 445 Ile Ser Ile Phe Leu His Leu Val Lys Ile Pro Thr His Arg His Ile 450 455 460 Lys Gly Gly Ser Cys Pro Lys Pro His Arg Leu Thr Asn Lys Gly Ile 465 470 475 480 Cys Ser Cys Gly Ala Phe Lys Val Pro Gly Val Lys Thr Ile Trp Lys 485 490 495 Arg Arg <210> 27 <211> 1677 <212> DNA <213> Lymphocytic choriomeningitis virus (mutant P52) <400> 27 atgtctttgt ccaaagaagt caaaagcttt cagtggacac aggcgttgag gagggagttg 60 cagagtttta catcagatgt aaaggctgcc gtcatcaagg acgcaaccag tcttctaaat 120 gggttggact tttctgaagt cagcaacgtt cagaggatca tgagaaagga aaggagggat 180 gataaagact tgcagagact caggagtctt aaccagactg tgcattctct tgttgatctg 240 aagtctacat caaagaaaaa tgttctgaaa gtgggaagac ttagtgcaga ggaattgatg 300 acccttgcag ctgatcttga gaagctgaag gccaaaatta tgagaactga gaggcctcaa 360 gcttctggag tctacatggg aaatttgaca gcacaacaac ttgatcaaag atcccaaata 420 ctgcaaatgg ttgggatgag aagacctcag cagggtgcaa gtggtgtagt aagggttttgg 480 gatgtgaagg actcatcact tctgaacaat cagttcggca caatgccaag cctgacaatg 540 gcttgcatgg caaaacgtc acagacccca ctcaatgatg ttgtgcaggc actcacagac 600 cttggcttac tttacacagt caaatacccg aatctcagtg atcttgaaag gctaaaggat 660 aaacacccag ttctgggggt cattactgaa cagcaatcta gtatcaatat ctctggttat 720 aatttcagtc ttggtgcagc tgtgaaagcg ggggcagctc tgctagatgg agggaacatg 780 ctggaatcta tcttgatcaa accgagcaac agtgaggatc tcctaaaagc agtctcggg 840 gccaagaaga aactcaacat gtttgtctca gatcaagttg gagatagaaa tccctatgaa 900 aacatccttt ataaagtctg tctttcaggt gaaggatggc catacatagc ctgtagaacg 960 tcagttgtgg ggagagcatg ggagaacaca aaattgatc tcaaaatga aaaacttgtt 1020 gccaactcat ctaggccagt gcctggagca gcaggcccac ctcaggtggg cttgagttac 1080 agtcagacaa tgctgttgaa agacttgatg ggagggattg atcccaatgc tcccacatgg 1140 attgacattg agggcaggtt caatgatcca gtggagatag caatattcca accaaaat 1200 gggcaattca tacattttta cagggaacct acggaccaga agcaattcaa gcaggactca 1260 aagtattcac acggcatgga tcttgctgat ctcttcaatg cacagcctgg gctgacctca 1320 tcagttatag gtgctctccc acaagggatg gttttgagct gtcaaggttc tgatgacatc 1380 agaaagcttc tggactcaca aaayagaagg gacataaaac tcattgatgt tgagatgacc 1440 aaagggcct caagagaata tgaagataaa gtgtgggaca aatatggctg gctatgcaaa 1500 atgcacactg gggtagtgag agaaaaaaag aagaaagaga tcaccccaca ctgtgcactc 1560 atggactgca tcatttttga gagtgcttcc aaggcaagac tccctgatct aaaaaccgtt 1620 caacacatcc tgccacatga tttaatcttc agaggaccca atgttgtgac actctaa 1677 <210> 28 <211> 558 <212> PRT <213> Lymphoma virus (mutant P52) <400> 28 Met Ser Leu Ser Lys Glu Val Lys Ser Phe Gln Trp Thr Gln Ala Leu 1 5 10 15 Arg Arg Glu Leu Gln Ser Phe Thr Ser Asp Val Lys Ala Ala Val Ile 20 25 30 Lys Asp Ala Thr Ser Leu Leu Asn Gly Leu Asp Phe Ser Glu Val Ser 35 40 45 Asn Val Gln Arg Ile Met Arg Lys Glu Arg Arg Asp Asp Lys Asp Leu 50 55 60 Gln Arg Leu Arg Ser Leu Asn Gln Thr Val His Ser Leu Val Asp Leu 65 70 75 80 Lys Ser Thr Ser Lys Lys Asn Val Leu Lys Val Gly Arg Leu Ser Ala 85 90 95 Glu Glu Leu Met Thr Leu Ala Ala Asp Leu Glu Lys Leu Lys Ala Lys 100 105 110 Ile Met Arg Thr Glu Arg Pro Gln Ala Ser Gly Val Tyr Met Gly Asn 115 120 125 Leu Thr Ala Gln Gln Leu Asp Gln Arg Ser Gln Ile Leu Gln Met Val 130 135 140 Gly Met Arg Arg Pro Gln Gln Gly Ala Ser Gly Val Val Arg Val Trp 145 150 155 160 Asp Val Lys Asp Ser Ser Leu Leu Asn Asn Gln Phe Gly Thr Met Pro 165 170 175 Ser Leu Thr Met Ala Cys Met Ala Lys Gln Ser Gln Thr Pro Leu Asn 180 185 190 Asp Val Val Gln Ala Leu Thr Asp Leu Gly Leu Leu Tyr Thr Val Lys 195 200 205 Tyr Pro Asn Leu Ser Asp Leu Glu Arg Leu Lys Asp Lys His Pro Val 210 215 220 Leu Gly Val Ile Thr Glu Gln Gln Ser Ser Ile Asn Ile Ser Gly Tyr 225 230 235 240 Asn Phe Ser Leu Gly Ala Ala Val Lys Ala Gly Ala Ala Leu Leu Asp 245 250 255 Gly Gly Asn Met Leu Glu Ser Ile Leu Ile Lys Pro Ser Asn Ser Glu 260 265 270 Asp Leu Leu Lys Ala Val Leu Gly Ala Lys Lys Lys Leu Asn Met Phe 275 280 285 Val Ser Asp Gln Val Gly Asp Arg Asn Pro Tyr Glu Asn Ile Leu Tyr 290 295 300 Lys Val Cys Leu Ser Gly Glu Gly Trp Pro Tyr Ile Ala Cys Arg Thr 305 310 315 320 Ser Val Val Gly Arg Ala Trp Glu Asn Thr Thr Ile Asp Leu Thr Asn 325 330 335 Glu Lys Leu Val Ala Asn Ser Ser Arg Pro Val Pro Gly Ala Ala Gly 340 345 350 Pro Pro Gln Val Gly Leu Ser Tyr Ser Gln Thr Met Leu Leu Lys Asp 355 360 365 Leu Met Gly Gly Ile Asp Pro Asn Ala Pro Thr Trp Ile Asp Ile Glu 370 375 380 Gly Arg Phe Asn Asp Pro Val Glu Ile Ala Ile Phe Gln Pro Gln Asn 385 390 395 400 Gly Gln Phe Ile His Phe Tyr Arg Glu Pro Thr Asp Gln Lys Gln Phe 405 410 415 Lys Gln Asp Ser Lys Tyr Ser His Gly Met Asp Leu Ala Asp Leu Phe 420 425 430 Asn Ala Gln Pro Gly Leu Thr Ser Ser Val Ile Gly Ala Leu Pro Gln 435 440 445 Gly Met Val Leu Ser Cys Gln Gly Ser Asp Asp Ile Arg Lys Leu Leu 450 455 460 Asp Ser Gln Asn Arg Arg Asp Ile Lys Leu Ile Asp Val Glu Met Thr 465 470 475 480 Lys Glu Ala Ser Arg Glu Tyr Glu Asp Lys Val Trp Asp Lys Tyr Gly 485 490 495 Trp Leu Cys Lys Met His Thr Gly Val Val Arg Asp Lys Lys Lys Lys 500 505 510 Glu Ile Thr Pro His Cys Ala Leu Met Asp Cys Ile Ile Phe Glu Ser 515 520 525 Ala Ser Lys Ala Arg Leu Pro Asp Leu Lys Thr Val His Asn Ile Leu 530 535 540 Pro His Asp Leu Ile Phe Arg Gly Pro Asn Val Val Thr Leu 545 550 555 <210> 29 <211> 273 <212> DNA <213> Lymphocytic choriomeningitis virus (mutant P52) <400> 29 atgggccaag gcaagtccaa agaagaaagg gacaccagca atacaggcag agcagagctt 60 ttgccagaca ccacctatct tggtcctcta aattgtaaat catgttggca gaaatttgac 120 agcttggtta gatgccatga ccactatctt tgcagacact gtctgaatct cctgctgtca 180 gtttccgaca gatgtcctct ctgtaagtat ccactgccaa ccaaactgaa ggtgtcaaca 240 gtcccaagct ccccacctcc ctatgaggag tga 273 <210> 30 <211> 90 <212> PRT <213> Lymphocytic choriomeningitis virus (mutant P52) <400> 30 Met Gly Gln Gly Lys Ser Lys Glu Glu Arg Asp Thr Ser Asn Thr Gly 1 5 10 15 Arg Ala Glu Leu Leu Pro Asp Thr Thr Tyr Leu Gly Pro Leu Asn Cys 20 25 30 Lys Ser Cys Trp Gln Lys Phe Asp Ser Leu Val Arg Cys His Asp His 35 40 45 Tyr Leu Cys Arg His Cys Leu Asn Leu Leu Leu Ser Val Ser Asp Arg 50 55 60 Cys Pro Leu Cys Lys Tyr Pro Leu Pro Thr Lys Leu Lys Val Ser Thr 65 70 75 80 Val Pro Ser Ser Pro Pro Pro Tyr Glu Glu 85 90 <210> 31 <211> 6630 <212> DNA <213> Lymphocytic choriomeningitis virus (mutant P52) <400> 31 atggatgaaa ctattgcaga tttgagagag ttgtgtctaa attacataga acaggacgag 60 aggctgtcaa ggcaaaaact caacttcctg ggacaaagag aacccagaat ggtgctaatt 120 gagggactca aattgttatc acgctgtata gagatagaca gtgcagacaa aagtggttgc 180 atacacaacc acgatgacaa atctgttgaa acaatcctaa tagactctgg gattgtgtgt 240 ccaggactgc cactcatcat ccctgatggt tataagttga ttgacaattc ccttattctt 300 cttgaatgtt ttgttagaag cacaccagct agttttgaaa agaagttcat tgaggacacc 360 aacaaactag catgcatcaa agaagatctt gctgttgcag gcatcacact ggttccaata 420 gtggatggtc gttgtgatta tgataacagt ttcatgccag aatgggtgaa ttttaagttc 480 agagacctcc tatttaaact cctggagtat tctagtcaag atgagaaagt ttttgaggag 540 tctgaatact tcaggctctg tgagtctctt aagaccactg ttgacaaacg ttccggcatg 600 gactcaatga aaatttgaa agacgcaaga tcatttcata acgatgagat tatgaaaatg 660 tgccacgatg gtgtcaaccc caacatgagt tgcgatgatg tggtctttgg cataaattcc 720 ttttttggca ggtttaggag ggacctgtta aatgggaaac tcaaaaggaa tttccaaaag 780 gtcagccctg ggggcttaat caaggaattc tctgaacttt atgaaaccct tactgataat 840 gatgacatat taatgttgag caaagaggca gttgaatcct gccccttaat gaggttcatt 900 acagcagaga cccatgggca tgagagagga agcgatgcta acactgagta tgaaaggcta 960 ctctctatgt tgaacaaggt gaaaagttta aaattattaa acactagaag gagacagctg 1020 ctgaacttag atgtcttatg tctttcttca cttattaagc agtcaatttc caaagggttg 1080 gaaaatgata aacattgggt tggttgttgc tacagtagtg tgaatgatag gcttgtgagc 1140 cttcaaagta ccaaagaaga attcatgaga cttttgaaga acagaagaaa atcaagagtg 1200 cacaaaaagg catctcttga tgagcttttt agggtatcca taaatgagtt catagcaaaa 1260 atccagaaat gcctatcaac agtgggactt agttttgagc attacggact atcagaatgc 1320 ctcgtgcaag aatgccatat accatttgct gaatttgaga actttatgag agccgggact 1380 catcctgtaa tgcattacac aaaatttgaa gattacactt tccagcctaa catagagcaa 1440 tgaggtt tacagattt gagaaaactg tcatctgttt gtttggttt aaaaacagc 1500 atgaaaaaaa gctcagttgc aaggttgaga cagaaccaac tgggtctgt gagatatca 1560 gtggtggagt gcaagaggt gttttgccag atataaaac tggattccga agagtatcat 1620 ctactatatc agaaaactgg agaatcatcg aggtgttatt ccatacaagg tccggatggt 1680 cacttgattt ccttttacgc agatccaaaa aggttcttt taccatttt ttcagatgag 1740 gtgttgcaca acatgataga cacaatgatt tcatggatta ggtcatgccc tgacttaaaa 1800 gattctctta ttgacattga gactgcacta aggacattga tcctactgat gctcaccac 1860 Chacaaaga Gaatcaaa GCAggttCA Attattaggt Atttagt ggccatcgtc 1920 tcagacttt catcgacctc attaatggat aagttgaagg aggatctaat cacacctgcc 1980 gagaaagtgg tgtacaggct gcttcggtttt tgattagga caatttttgg tactggtgaa 2040 aaggtgttat tgagtgcaaa attcaagtttt atgttgaatg trtcatacct gtgtcatttg 2100 atcacaagg agacccctga tagattgaca gatcagataa atgttttga aaagttcttt 2160 gagcccaaga gtgagtttgg tttctttgtc aaccctaagg aaacaatcac acccgaagag 2220 gaatgtgttt tttatgaaca aatgaagaag ttcaccggta aagatattga ttgtcagcat 2280 tcaacccctg gtgttaattt agagatcttt agcatgatgg tatcttcatt caacaatggc 2340 accttaattc taaaagggga gaaaaggctc aacaatctgg accccacatgac caactctgga 2400 tgtgcgacag cattagatct cgcaagcaac aaaagtgtgg ttgtcaataa acatctgaat 2460 ggagaacggc ttttggagta tgattttaac aaattgcttg ttagtgctgt gagccaaatt 2520 acagagggct tcatgaggaa acaaaagtat aagctgagac actcagatta cgaatataag 2580 gtctcaaagc ttgtctctag attagtcatc ggttccagga aaacagaagt agacaaattg 2640 gaagatgatc cggtagatgt gtgtttcgag ggggaggagg agacaagttt tttcaggagt 2700 ttagaagata aggtcagctc cacaataaca cggtataata gaggcactag gcttaatgaa 2760 gggcaagggg agggagaatt caagaacaca aaaggactac accaccttca gattattttg 2820 tcaggtaaaa gagcttatct gaggaaagtc attttatcag aaatttcatt tcatctagta 2880 gaggactttg atccatcctg tctcaccaat gacgacatga ggtttatttg tgaggctgtt 2940 gaaggttcaa cagaactgtc accattgtat tttacatcag ctgtcaaaga acaatgtggt 3000 ctggatgaga tggcaagaaa cctctgtaga aagttcttct cagagggtga ttggttctca 3060 tgtatgaaga tgatcttgtt acagatgaat gcaaatgcgt attcagggaa gtacagacac 3120 atgcagaggc agagcttaaa ttttaaattt gactgggaca aattggaaga agatgtaaga 3180 attagtgaaa gggaaagcaa ttctgaatct ctaagtaagg ccctttcatt gacaaaatgc 3240 atgagtgctg ctctaaagaa tctgtgtttt tactcagaag aatcaccaac atcatacact 3300 tcagttggcc ctgactctgg gagactaaaa tttgcattgt catacaaaga gcaggttggg 3360 ggaatagag agctttacat tggggatttg aggacaaaaa tgttcacaag attggtagaa 3420 gattattttg aatccttttc tagtttctt tcaggatctt gttaaacaa tgacaaagag 3480 tttgaaaatg caatcttgtc aatgactatc aatgtgagag aagggttgtt aaactacagc 3540 atggatcaca gcaaatgggg accaatgatg tgcccattcc tattcttaat gcttctccaa 3600 aatctcaaac tgggtgatga tcagtacgtg cgttctggaa aagatcatgt tagcaccttg 3660 ttgacttggc atatgcataa acttgttgaa gtccctttcc ctgttgtgaa tgcaatgatg 3720 aaatcatatg ttaaatcaaa actcaagctt ctcaaagggt caggaacgac tgttacggag 3780 agaatcttta gagagtattt tgaaatgggg gtggtgccat ctcacatatc tagtctcatt 3840 gacatgggac aggggatcct acacaatgct tctgattttt acggtttaat tagtgaaagg 3900 tttatcaatt attgtattgg tgtcattttt ggagagaggc cagaagccta tacatcaagt 3960 gatgatcaga tcactttatt tgacaagaga ttgagtgact tagttgatag tgacccagaa 4020 gaagtccttg tcttgctgga attccactct cacttaagtg gtttgttgaa caagttcatc 4080 agtccaaaaa gtgtggttgg gcggtttgca gcggaattca aatccagatt ttatgtgtgg 4140 ggggaggagg tccctctcct cacgaaattt gtgtctgcgg cactacacaa tgttaagtgt 4200 aaagaaccgc atcaactttg tgagacaata gatacgattg ctgatcaagc tatagcaaat 4260 ggagttccag tttttttagt aaactgtatc cagaggagga cactggatct cttgaaatat 4320 gctaatttcc ctttagatcc attcttgtta aacactcaca ctgatgtaaa ggattggtta 4380 gatggttcta gaggttatag atccaaga ctcattgaag aattgtgtcc cagtgaaaca 4440 aagatcatga gaaacttgt aagaacta catcacaac tcagaacgg tgaatgtaac 4500 gaggaatttt ttcagacct cttcacagg gaaagaaag agccattcct tcattggga 4560 gagattcttg gtcttgagga tgatcttaat gagttggcaa gcatcattg gttgaatctg 4620 aatgaaatgt tcccattgag gatggttctg agacaaaag tggtttaccc atcagtaatg 4680 accttcaag aggaaagat cccctcattg attaaaacc tccaaaataa gctttgtagt 4740 aagttcaca gaggtgcaca gaagctgttg tcagaggcaa tcaaatc agcttttcag 4800 agttgtgtct catccggctt tataggtctc tgtaagactt taggagtag gtgtgtgaga 4860 aaaaaaaca gggaaaatat gtatatcaga aaggtgcttg aagatctgac catggatgaa 4920 catgtcaca gggttcacaa acatttgt gtgatgttgt acatttgcga caacagaga 4980 cacccagagg ctcaccgtga ccacatcaac ctttgaggc cccttctctg ggactacatt 5040 tgcatctcat tgagcaactc ttttgagctg ggtgtttggg ttttagcaga acctgtgaaa 5100 ggaaagaacg agagtaattc ggctgttagg cacttaaatc catgtgatta tgtagcaaga 5160 aaacctgaga gttcgagact actagaggat aaagtgagtt tgaatcatgt aattcaatct 5220 gtgaggcgac tgtaccccaa aatctttgag gatcagttgc tcccattcat gtctgatgtg 5280 agctcaaaaa atatgagatg gagtcccagg attaaattcc ttgacctttg tgtgctgatt 5340 gacatcaact cagagtcttt gtcactcatt tctcatgttg tcaaatggaa gagggacgaa 5400 cattacactg tgctgttttc tgatctcgtc aactctcacc aacggtcaga ctcaagttta 5460 gttgatgaat ttgttgtcag cacaagggat gtctgcaaga actttttgaa gcaagtgtat 5520 ttcgaatcat ttgtacgaga gtttgttgca acagctagga ccttaggtaa cttttcatgg 5580 ttcccccata aggacatgat gccatctgaa gatggcgctg aagcactggg acccttccaa 5640 tcatttattt tgaaagtggt gaacaagaaa atagagaggc ccatgtttag gaatgacttg 5700 cagtttggtt ttggttggtt ctcttatcgt gtgggggatg ttgtgtgtaa tgccgctatg 5760 ttaattaagc agggtttgac agatccaaaa gcatttaaat ctttaagaga tttgtgggat 5820 tacatgctca gcagcacaga ggggatattg gagttctcaa tcacagtgga tttcacacac 5880 aaccagaaca acactgactg cttgaggaaa ttttcattga tctttgtggt taaatgccaa 5940 ttacagagtc caggtgtagc tgattactta tcgtgctctc attccttcaa aggtgaggtt 6000 gacaggagat tattagatga gtgtctcaat ctgttgagga cagaccccat ctttaaagcg 6060 aatgatggag tctttgacat taggtctgaa gagtttgaag attacatgga agaccctttg 6120 acacttggtg attcactaga acttgaacta ataggttcta gaaggattct gaatgagatc 6180 aaatctactg actttgagag gatagggcct gagtgggaac ctgtgcctct gaccataagg 6240 aagggtgccc tctttgaggg gaggaacttt gttcagaatr tctctgtgaa attggagaca 6300 aaggacatga gggtctttct ggcagagctc gagggctgtg gaaaaattgg tgatgtcctc 6360 ggcagcctcc tcctgcaccg attcagaact ggtgagcact tgatggagtc agaaataagt 6420 rcagttcttc aggagctctg catggacaga tccgtcatgc tgacaccatt atcttttgtg 6480 ccagattggt tcaccttcag agattgtagg ctctgcttca gcaggtcaaa gaacactgta 6540 atgtatgaga caactggggg caggttcaga ctcaagggga aatcctgtga cgattggctg 6600 gcggagcggg tggccgagga gatcgactag 6630 <210> 32 <211> 2209 <212> PRT <213> Lymphocytic choriomeningitis virus (mutant P52) <220> <221> MISC_FEATURE <222> (2094)..(2094) <223> Xaa can be Ile or Val <220> <221> MISC_FEATURE <222> (2141)..(2141) <223> Xaa can be Thr or Ala <400> 32 Met Asp Glu Thr Ile Ala Asp Leu Arg Glu Leu Cys Leu Asn Tyr Ile 1 5 10 15 Glu Gln Asp Glu Arg Leu Ser Arg Gln Lys Leu Asn Phe Leu Gly Gln 20 25 30 Arg Glu Pro Arg Met Val Leu Ile Glu Gly Leu Lys Leu Leu Ser Arg 35 40 45 Cys Ile Glu Ile Asp Ser Ala Asp Lys Ser Gly Cys Ile His Asn His 50 55 60 Asp Asp Lys Ser Val Glu Thr Ile Leu Ile Asp Ser Gly Ile Val Cys 65 70 75 80 Pro Gly Leu Pro Leu Ile Ile Pro Asp Gly Tyr Lys Leu Ile Asp Asn 85 90 95 Ser Leu Ile Leu Leu Glu Cys Phe Val Arg Ser Thr Pro Ala Ser Phe 100 105 110 Glu Lys Lys Phe Ile Glu Asp Thr Asn Lys Leu Ala Cys Ile Lys Glu 115 120 125 Asp Leu Ala Val Ala Gly Ile Thr Leu Val Pro Ile Val Asp Gly Arg 130 135 140 Cys Asp Tyr Asp Asn Ser Phe Met Pro Glu Trp Val Asn Phe Lys Phe 145 150 155 160 Arg Asp Leu Leu Phe Lys Leu Leu Glu Tyr Ser Ser Gln Asp Glu Lys 165 170 175 Val Phe Glu Glu Ser Glu Tyr Phe Arg Leu Cys Glu Ser Leu Lys Thr 180 185 190 Thr Val Asp Lys Arg Ser Gly Met Asp Ser Met Lys Ile Leu Lys Asp 195 200 205 Ala Arg Ser Phe His Asn Asp Glu Ile Met Lys Met Cys His Asp Gly 210 215 220 Val Asn Pro Asn Met Ser Cys Asp Asp Val Val Phe Gly Ile Asn Ser 225 230 235 240 Phe Phe Gly Arg Phe Arg Arg Asp Leu Leu Asn Gly Lys Leu Lys Arg 245 250 255 Asn Phe Gln Lys Val Ser Pro Gly Gly Leu Ile Lys Glu Phe Ser Glu 260 265 270 Leu Tyr Glu Thr Leu Thr Asp Asn Asp Asp Ile Leu Met Leu Ser Lys 275 280 285 Glu Ala Val Glu Ser Cys Pro Leu Met Arg Phe Ile Thr Ala Glu Thr 290 295 300 His Gly His Glu Arg Gly Ser Asp Ala Asn Thr Glu Tyr Glu Arg Leu 305 310 315 320 Leu Ser Met Leu Asn Lys Val Lys Ser Leu Lys Leu Leu Asn Thr Arg 325 330 335 Arg Arg Gln Leu Leu Asn Leu Asp Val Leu Cys Leu Ser Ser Leu Ile 340 345 350 Lys Gln Ser Ile Ser Lys Gly Leu Glu Asn Asp Lys His Trp Val Gly 355 360 365 Cys Cys Tyr Ser Ser Val Asn Asp Arg Leu Val Ser Leu Gln Ser Thr 370 375 380 Lys Glu Glu Phe Met Arg Leu Leu Lys Asn Arg Arg Lys Ser Arg Val 385 390 395 400 His Lys Lys Ala Served Asp Glu To Phe Arg Val Served Ile Asn Glu 405 410 415 Phe and Ala Lys and Gln Lys Cys can be found in Thr Val Gly 420 425 430 Glu His Tyr Gly Leu Ser Glu Cys Leu Val Gln Glu Cys His Ile Pro 435 440 445 Phe Ala Glu Phe Glu Asn Phe Met Arg Ala Gly Thr His Pro Val Met 450 455 460 His Tyr Thr Lys Phe Glu Asp Tyr Thr Phe Gln Pro Asn Ile Glu Gln 465 470 475 480 Leu Arg Gly Leu Gln Ser Leu Arg Leu Ser Val Cys Leu Wing 485,490,495 Leu Thr Asn Will Be Met Lys Thr Will Be Val Ala Arg Leu Arg Gln Asn 500 505 510 Gln Leu Gly Ser Val Arg Tyr Gln Val Val Glu Cys Lys Glu Val Phe 515,520,525 Cys Gln Ile Ile Lys Leu Asp Ser Glu Glu Tyr His Leu Tyr Gln 530 535 540 Lys Thr Gly Glu Ser Ser Arg Cys Tyr Ser Ile Gln Gly Pro Asp Gly 545 550 555 560 His Leu Ile Ser Phe Tyr Ala Asp Pro Lys Arg Phe Phe Leu Pro Ile 565 570 575 Phe Ser Asp Glu Val Leu His Asn Met Ile Asp Thr Met Ile Ser Trp 580 585 590 Ile Arg Ser Cys Pro Asp Leu Lys Asp Ser Leu Ile Asp Ile Glu Thr 595 600 605 Ala Leu Arg Thr Leu Ile Leu Leu Met Leu Thr Asn Pro Thr Lys Arg 610 615 620 Asn Gln Lys Gln Val Gln Asn Ile Arg Tyr Leu Val Met Ala Ile Val 625 630 635 640 Ser Asp Phe Ser Ser Thr Ser Leu Met Asp Lys Leu Lys Glu Asp Leu 645 650 655 Ile Thr Pro Ala Glu Lys Val Val Tyr Arg Leu Leu Arg Phe Leu Ile 660 665 670 Arg Thr Ile Phe Gly Thr Gly Glu Lys Val Leu Leu Ser Ala Lys Phe 675 680 685 Lys Phe Met Leu Asn Val Ser Tyr Leu Cys His Leu Ile Thr Lys Glu 690 695 700 Thr Pro Asp Arg Leu Thr Asp Gln Ile Lys Cys Phe Glu Lys Phe Phe 705 710 715 720 Glu Pro Lys Ser Glu Phe Gly Phe Phe Val Asn Pro Lys Glu Thr Ile 725 730 735 Thr Pro Glu Glu Glu Cys Val Phe Tyr Glu Gln Met Lys Lys Phe Thr 740 745 750 Gly Lys Asp Ile Asp Cys Gln His Ser Thr Pro Gly Val Asn Leu Glu 755 760 765 Ile Phe Ser Met Met Val Ser Ser Phe Asn Asn Gly Thr Leu Ile Leu 770 775 780 Lys Gly Glu Lys Arg Leu Asn Asn Leu Asp Pro Met Thr Asn Ser Gly 785 790 795 800 Cys Ala Thr Ala Leu Asp Leu Ala Ser Asn Lys Ser Val Val Val Asn 805 810 815 Lys His Leu Asn Gly Glu Arg Leu Leu Glu Tyr Asp Phe Asn Lys Leu 820 825 830 Leu Val Ser Ala Val Ser Gln Ile Thr Glu Gly Phe Met Arg Lys Gln 835 840 845 Lys Tyr Lys Leu Arg His Ser Asp Tyr Glu Tyr Lys Val Ser Lys Leu 850 855 860 Val Ser Arg Leu Val Ile Gly Ser Arg Lys Thr Glu Val Asp Lys Leu 865 870 875 880 Glu Asp Asp Pro Val Asp Val Cys Phe Glu Gly Glu Glu Glu Thr Ser 885 890 895 Phe Phe Arg Ser Leu Glu Asp Lys Val Ser Ser Thr Ile Thr Arg Tyr 900 905 910 Asn Arg Gly Thr Arg Leu Asn Glu Gly Gln Gly Glu Gly Glu Phe Lys 915 920 925 Asn Thr Lys Gly Leu His His Leu Gln Ile Ile Leu Ser Gly Lys Arg 930 935 940 Ala Tyr Leu Arg Lys Val Ile Leu Ser Glu Ile Ser Phe His Leu Val 945 950 955 960 Glu Asp Phe Asp Pro Ser Cys Leu Thr Asn Asp Asp Met Arg Phe Ile 965 970 975 Cys Glu Ala Val Glu Gly Ser Thr Glu Leu Ser Pro Leu Tyr Phe Thr 980 985 990 Ser Ala Val Lys Glu Gln Cys Gly Leu Asp Glu Met Ala Arg Asn Leu 995 1000 1005 Cys Arg Lys Phe Phe Ser Glu Gly Asp Trp Phe Ser Cys Met Lys 1010 1015 1020 Met Ile Leu Gln With Asn Only Asn Only Tyr Ser Gly Lys Tyr 1025 1030 1035 Arg His Met Gln Arg Gln Ser Leu Asn Phe Lys Phe Asp Trp Asp 1040 1045 1050 Lys Leu Glu Glu Asp Val Arg Ile Ser Glu Arg Glu Ser Asn Ser 1055 1060 1065 Glu Ser Leu Ser Lys Ala Leu Ser Thr Lys Cys Met Ser Ala 1070 1075 1080 Ala Leu Lys Asn Leu Cys Phe Tyr Ser Glu Glu Ser Pro Thr Ser 1085 1090 1095 Tyr Thr Ser Val Gly Pro Asp Ser Gly Arg Leu Lys Phe Ala Leu 1100 1105 1110 Tyr Lys Gln Val Gly Gly Asn Arg Glu Leu Tyr Ile Gly 1115 1120 1125 Asp Leu Arg Thr Lys Met Phe Thr Arg Leu Val Glu Asp Tyr Phe 1130 1135 1140 Glu Ser PhE Ser PHE PHE Ser Gly Ser Cys Leu Asn Asn Asp 1145 1150 1155 Lys Glu Phe Glu Asn Ala Ile Leu Ser Met Thr Ile Asn Val Arg 1160 1165 1170 Glu Gly Leu Leu Asn Tyr Ser Met Asp His Ser Lys Trp Gly Pro 1175 1180 1185 Met Met Cys Pro Phe Leu Phe Leu Met Leu Leu Gln Asn Leu Lys 1190 1195 1200 Leu Gly Asp Asp Gln Tyr Val Arg Ser Gly Lys Asp His Val Ser 1205 1210 1215 Thr Leu Leu Thr Trp His Met His Lys Leu Val Glu Val Pro Phe 1220 1225 1230 Pro Val Val Asn Ala Met Met Lys Ser Tyr Val Lys Ser Lys Leu 1235 1240 1245 Lys Leu Leu Lys Gly Ser Gly Thr Thr Val Thr Glu Arg Ile Phe 1250 1255 1260 Arg Glu Tyr Phe Glu Met Gly Val Val Pro Ser His Ile Ser Ser 1265 1270 1275 Leu Ile Asp Met Gly Gln Gly Ile Leu His Asn Ala Ser Asp Phe 1280 1285 1290 Tyr Gly Leu Ile Ser Glu Arg Phe Ile Asn Tyr Cys Ile Gly Val 1295 1300 1305 Ile Phe Gly Glu Arg Pro Glu Ala Tyr Thr Ser Ser Asp Asp Gln 1310 1315 1320 Ile Thr Leu Phe Asp Lys Arg Leu Ser Asp Leu Val Asp Ser Asp 1325 1330 1335 Pro Glu Glu Val Leu Val Leu Leu Glu Phe His Ser His Leu Ser 1340 1345 1350 Gly Leu Leu Asn Lys Phe Ile Ser Pro Lys Ser Val Val Gly Arg 1355 1360 1365 Phe Ala Ala Glu Phe Lys Ser Arg Phe Tyr Val Trp Gly Glu Glu 1370 1375 1380 Val Pro Leu Leu Thr Lys Phe Val Ser Ala Ala Leu His Asn Val 1385 1390 1395 Lys Cys Lys Glu Pro His Gln Leu Cys Glu Thr Ile Asp Thr Ile 1400 1405 1410 Ala Asp Gln Ala Ile Ala Asn Gly Val Pro Val Phe Leu Val Asn 1415 1420 1425 Cys Ile Gln Arg Arg Thr Leu Asp Leu Leu Lys Tyr Ala Asn Phe 1430 1435 1440 Pro Leu Asp Pro Phe Leu Leu Asn Thr His Thr Asp Val Lys Asp 1445 1450 1455 Trp Leu Asp Gly Ser Arg Gly Tyr Arg Ile Gln Arg Leu Ile Glu 1460 1465 1470 Glu Leu Cys Pro Ser Glu Thr Lys Ile Met Arg Lys Leu Val Arg 1475 1480 1485 Arg Leu His His Lys Leu Lys Asn Gly Glu Cys Asn Glu Glu Phe 1490 1495 1500 Phe Leu Asp Leu Phe Asn Arg Glu Lys Lys Glu Ala Ile Leu Gln 1505 1510 1515 Leu Gly Glu Ile Leu Gly Leu Glu Asp Asp Leu Asn Glu Leu Ala 1520 1525 1530 Ser Ile Asn Trp Leu Asn Leu Asn Glu Met Phe Pro Leu Arg Met 1535 1540 1545 Val Leu Arg Gln Lys Val Val Tyr Pro Ser Val Met Thr Phe Gln 1550 1555 1560 Glu Glu Lys Ile Pro Ser Leu Ile Lys Thr Leu Gln Asn Lys Leu 1565 1570 1575 Cys Ser Lys Phe Thr Arg Gly Ala Gln Lys Leu Leu Ser Glu Ala 1580 1585 1590 Ile Asn Lys Ser Ala Phe Gln Ser Cys Val Ser Ser Gly Phe Ile 1595 1600 1605 Gly Leu Cys Lys Thr Leu Gly Ser Arg Cys Val Arg Asn Lys Asn 1610 1615 1620 Arg Glu Asn Met Tyr Ile Arg Lys Val Leu Glu Asp Leu Thr Met 1625 1630 1635 Asp Glu His Val Thr Arg Val His Lys Gln Asp Gly Val Met Leu 1640 1645 1650 Tyr Ile Cys Asp Lys Gln Arg His Pro Glu Ala His Arg Asp His 1655 1660 1665 Ile Asn Leu Leu Arg Pro Leu Leu Trp Asp Tyr Ile Cys Ile Ser 1670 1675 1680 Leu Ser Asn Ser Phe Glu Leu Gly Val Trp Val Leu Ala Glu Pro 1685 1690 1695 Val Lys Gly Lys Asn Glu Ser Asn Ser Ala Val Arg His Leu Asn 1700 1705 1710 Pro Cys Asp Tyr Val Ala Arg Lys Pro Glu Ser Ser Arg Leu Leu 1715 1720 1725 Glu Asp Lys Val Ser Leu Asn His Val Ile Gln Ser Val Arg Arg 1730 1735 1740 Leu Tyr Pro Lys Ile Phe Glu Asp Gln Leu Leu Pro Phe Met Ser 1745 1750 1755 Asp Val Ser Ser Lys Asn Met Arg Trp Ser Pro Arg Ile Lys Phe 1760 1765 1770 Leu Asp Leu Cys Val Leu Ile Asp Ile Asn Ser Glu Ser Leu Ser 1775 1780 1785 Leu Ile Ser His Val Val Lys Trp Lys Arg Asp Glu His Tyr Thr 1790 1795 1800 Val Leu Phe Ser Asp Leu Val Asn Ser His Gln Arg Ser Asp Ser 1805 1810 1815 Ser Leu Val Asp Glu Phe Val Val Ser Thr Arg Asp Val Cys Lys 1820 1825 1830 Asn Phe Leu Lys Gln Val Tyr Phe Glu Ser Phe Val Arg Glu Phe 1835 1840 1845 Val Ala Thr Ala Arg Thr Leu Gly Asn Phe Ser Trp Phe Pro His 1850 1855 1860 Lys Asp Met Met Pro Ser Glu Asp Gly Ala Glu Ala Leu Gly Pro 1865 1870 1875 Phe Gln Ser Phe Ile Leu Lys Val Val Asn Lys Lys Ile Glu Arg 1880 1885 1890 Pro Met Phe Arg Asn Asp Leu Gln Phe Gly Phe Gly Trp Phe Ser 1895 1900 1905 Tyr Arg Val Gly Asp Val Val Cys Asn Ala Ala Met Leu Ile Lys 1910 1915 1920 Gln Gly Leu Thr Asp Pro Lys Ala Phe Lys Ser Leu Arg Asp Leu 1925 1930 1935 Trp Asp Tyr Met Leu Ser Ser Thr Glu Gly Ile Leu Glu Phe Ser 1940 1945 1950 Ile Thr Val Asp Phe Thr His Asn Gln Asn Asn Thr Asp Cys Leu 1955 1960 1965 Arg Lys Phe Ser Leu Ile Phe Val Val Lys Cys Gln Leu Gln Ser 1970 1975 1980 Pro Gly Val Ala Asp Tyr Leu Ser Cys Ser His Ser Phe Lys Gly 1985 1990 1995 Glu Val Asp Arg Arg Leu Leu Asp Glu Cys Leu Asn Leu Leu Arg 2000 2005 2010 Thr Asp Pro Ile Phe Lys Ala Asn Asp Gly Val Phe Asp Ile Arg 2015 2020 2025 Ser Glu Glu Phe Glu Asp Tyr Met Glu Asp Pro Leu Thr Leu Gly 2030 2035 2040 Asp Ser Leu Glu Leu Glu Leu Ile Gly Ser Arg Arg Ile Leu Asn 2045 2050 2055 Glu Ile Lys Ser Thr Asp Phe Glu Arg Ile Gly Pro Glu Trp Glu 2060 2065 2070 Pro Val Pro Leu Thr Ile Arg Lys Gly Ala Leu Phe Glu Gly Arg 2075 2080 2085 Asn Phe Val Gln Asn Xaa Ser Val Lys Leu Glu Thr Lys Asp Met 2090 2095 2100 Arg Val Phe Leu Ala Glu Leu Glu Gly Cys Gly Lys Ile Gly Asp 2105 2110 2115 Val Leu Gly Ser Leu Leu Leu His Arg Phe Arg Thr Gly Glu His 2120 2125 2130 Leu Met Glu Ser Glu Ile Ser Xaa Val Leu Gln Glu Leu Cys Met 2135 2140 2145 Asp Arg Ser Val Met Leu Thr Pro Leu Ser Phe Val Pro Asp Trp 2150 2155 2160 Phe Thr Phe Arg Asp Cys Arg Leu Cys Phe Ser Arg Ser Lys Asn 2165 2170 2175 Thr Val Met Tyr Glu Thr Thr Gly Gly Arg Phe Arg Leu Lys Gly 2180 2185 2190 Lys Ser Cys Asp Asp Trp Leu Ala Glu Arg Val Ala Glu Glu Ile 2195 2200 2205 Asp <210> 33 <211> 1497 <212> DNA <213> Lymphocytic choriomeningitis virus (mutant P91) <400> 33 atgggtcaga ttgtgacaat gtttgaggct ttgcctcaca tcattgatga ggtcatcaac 60 attgtcatta ttgtgctcat tataatcacg agcatcaaag ctgtgtacaa tttcgccacc 120 tgtgggatat tagcactggt cagcttcctt tttttggctg gtaggtcctg tggcatgtac 180 ggccttaatg gtcccgacat ctataaaggg gtttaccagt tcaaatcagt ggagtttgat 240 atgtctcact taaatctgac gatgcccaat gcgtgctcag ccaacaactc tcatcactac 300 atcagtatgg gaagctctgg actggagcta actttcacta acgactccat ccttaatcac 360 aatttttgca acttaacctc cgctttcaac aaaaagactt ttgaccatac actcatgagt 420 atagtctcga gtctgcacct cagtattaga gggaattcca accacaaagc agtgtcttgt 480 gattttaaca atggcatcac cattcaatac aacttgtcat tttcggaccc acagagcgct 540 atgagccagt gttggacttt cagaggtaga gtcttggaca tgtttagaac tgcctttgga 600 ggaaaataca tgagagtgg ctggggctgg gcaggttcag atggcagac cacttggtgc 660 agccaaacaa gctatcagta cctaatcata siaaacagga cttgggaaaa ccactgtaga 720 tatgcaggcc cttttgggat gtctagaatc ctctttgctc aggaaagac aaagtttctc 780 actaggagac ttgcaggcac attcacctgg accctgtcag actcctcagg agtagaaaat 840 ccaggtggtt attgcctgac caatggatg atccttgctg cagagctca atgttttggg 900 atacagctg ttgcaaatg taatgtcaat catgatgaag agttctgtga catgctacga 960 ctaattgatt acaaaggc cgccctgagt aagttcaagc aagatgtaga gtctgccttg 1020 catgtattca aaaacagt aaattctctg atttccgatc agctgttgat gaggaatcat 1080 ctaagagatc taatgggggt accatactgt aattactcaa agttctggta tctggaacat 1140 gctaagactg gtgagactag tgtacccaag tgctggcttg tcactaatgg ctcctacttg 1200 aatgagaccc actttagtga tcaatcgaaaaccag atacatgat acttagtg 1260 ttgaggagg actacataaa aagacaaggg agtactcctt tagccttaat ggatctttg 1320 atgttttcaa catcagcata tctaatcagc atctttctgc atcttgtgaa gataccaaca 1380 catagacaca taaagggcgg ttcatgtcca aagccacaccc gcttgaccaa caaggggatc 1440 tgtagttgtg gtgcattcaa ggtgcctggt gtaaaaacta tctggaaaag acgctga 1497 <210> 34 <211> 498 <212> PRT <213> Lymphocytic choriomeningitis virus (mutant P91) <400> 34 Met Gly Gln Ile Val Thr Met Phe Glu Ala Leu Pro His Ile Ile Asp 1 5 10 15 Glu Val Ile Asn Ile Val Ile Ile Val Leu Ile Ile Ile Thr Ser Ile 20 25 30 Lys Ala Val Tyr Asn Phe Ala Thr Cys Gly Ile Leu Ala Leu Val Ser 35 40 45 Phe Leu Phe Leu Ala Gly Arg Ser Cys Gly Met Tyr Gly Leu Asn Gly 50 55 60 Pro Asp Ile Tyr Lys Gly Val Tyr Gln Phe Lys Ser Val Glu Phe Asp 65 70 75 80 Met Ser His Leu Asn Leu Thr Met Pro Asn Ala Cys Ser Ala Asn Asn 85 90 95 Ser His His Tyr Ile Ser Met Gly Ser Ser Gly Leu Glu Leu Thr Phe 100 105 110 Thr Asn Asp Ser Ile Leu Asn His Asn Phe Cys Asn Leu Thr Ser Ala 115 120 125 Phe Asn Lys Lys Thr Phe Asp His Thr Leu Met Ser Ile Val Ser Ser 130 135 140 Leu His Leu Ser Ile Arg Gly Asn Ser Asn His Lys Ala Val Ser Cys 145 150 155 160 Asp Phe Asn Asn Gly Ile Thr Ile Gln Tyr Asn Leu Ser Phe Ser Asp 165 170 175 Pro Gln Ser Ala Met Ser Gln Cys Trp Thr Phe Arg Gly Arg Val Leu 180 185 190 Asp Met Phe Arg Thr Ala Phe Gly Gly Lys Tyr Met Arg Ser Gly Trp 195 200 205 Gly Trp Ala Gly Ser Asp Gly Lys Thr Thr Trp Cys Ser Gln Thr Ser 210 215 220 Tyr Gln Tyr Leu Ile Ile Gln Asn Arg Thr Trp Glu Asn His Cys Arg 225 230 235 240 Tyr Ala Gly Pro Phe Gly Met Ser Arg Ile Leu Phe Ala Gln Glu Lys 245 250 255 Thr Lys Phe Leu Thr Arg Arg Leu Ala Gly Thr Phe Thr Trp Thr Leu 260 265 270 Ser Asp Ser Ser Gly Val Glu Asn Pro Gly Gly Tyr Cys Leu Thr Lys 275 280 285 Trp Met Ile Leu Ala Ala Glu Leu Lys Cys Phe Gly Asn Thr Ala Val 290 295 300 Ala Lys Cys Asn Val Asn His Asp Glu Glu Phe Cys Asp Met Leu Arg 305 310 315 320 Leu Ile Asp Tyr Asn Lys Ala Ala Leu Ser Lys Phe Lys Gln Asp Val 325 330 335 Glu Ser Ala Leu His Val Phe Lys Thr Thr Val Asn Ser Leu Ile Ser 340 345 350 Asp Gln Leu Leu Met Arg Asn His Leu Arg Asp Leu Met Gly Val Pro 355 360 365 Tyr Cys Asn Tyr Ser Lys Phe Trp Tyr Leu Glu His Ala Lys Thr Gly 370 375 380 Glu Thr Ser Val Pro Lys Cys Trp Leu Val Thr Asn Gly Ser Tyr Leu 385 390 395 400 Asn Glu Thr His Phe Ser Asp Gln Ile Glu Gln Glu Ala Asp Asn Met 405 410 415 Ile Thr Glu Met Leu Arg Lys Asp Tyr Ile Lys Arg Gln Gly Ser Thr 420 425 430 Pro Leu Ala Leu Met Asp Leu Leu Met Phe Ser Thr Ser Ala Tyr Leu 435 440 445 Ile Ser Ile Phe Leu His Leu Val Lys Ile Pro Thr His Arg His Ile 450 455 460 Lys Gly Gly Ser Cys Pro Lys Pro His Arg Leu Thr Asn Lys Gly Ile 465 470 475 480 Cys Ser Cys Gly Ala Phe Lys Val Pro Gly Val Lys Thr Ile Trp Lys 485 490 495 Arg Arg <210> 35 <211> 1677 <212> DNA <213> Lymphocytic choriomeningitis virus (mutant P91) <400> 35 atgtctttgt ccaaagaagt caaaagcttt cagtggacac aggcgttgag gagggagttg 60 cagagtttta catcagatgt aaaggctgcc gtcatcaagg acgcaaccag tcttctaaat 120 gggttggact tttctgaagt cagcaacgtt cagaggatca tgagaaagga aaggagggat 180 gataaagact tgcagagact caggagtctt aaccagactg tgcattctct tgttgatctg 240 aagtctacat caaagaaaaa tgttctgaaa gtgggaagac ttagtgcaga ggaattgatg 300 acccttgcag ctgatcttga gaagctgaag gccaaaatta tgagaactga gaggcctcaa 360 gcttctggag tctacatggg aaatttgaca gcacaacaac ttgatcaaag atcccaaata 420 ctgcaaatgg ttgggatgag aagacctcag cagggtgcaa gtggtgtagt aagggttttgg 480 gatgtgaagg actcatcact tctgaacaat cagttcggca caatgccaag cctgacaatg 540 gcttgcatgg caaaacgtc acagacccca ctcaatgatg ttgtgcaggc actcacagac 600 cttggcttac tttacacagt caaatacccg aatctcagtg atcttgaaag gctaaaggat 660 aaacacccag ttctgggggt cattactgaa cagcaatcta gtatcaatat ctctggttat 720 aatttcagtc ttggtgcagc tgtgaaagcg ggggcagctc tgctagatgg agggaacatg 780 ctggaatcta tcttgatcaa accgagcaac agtgaggatc tcctaaaagc agtctcggg 840 gccaagaaga aactcaacat gtttgtctca gatcaagttg gagatagaaa tccctatgaa 900 aacatccttt ataaagtctg tctttcaggt gaaggatggc catacatagc ctgtagaacg 960 tcagttgtgg ggagagcatg ggagaacaca aaattgatc tcaaaatga aaaacttgtt 1020 gccaactcat ctaggccagt gcctggagca gcaggcccac ctcaggtggg cttgagttac 1080 agtcagacaa tgctgttgaa agacttgatg ggagggattg atcccaatgc tcccacatgg 1140 attgacattg agggcaggtt caatgatcca gtggagatag caatattcca accaaaat 1200 gggcaattca tacattttta cagggaacct acggaccaga agcaattcaa gcaggactca 1260 aagtattcac acggcatgga tcttgctgat ctcttcaatg cacagcctgg gctgacctca 1320 tcagttatag gtgctctccc acaagggatg gttttgagct gtcaaggttc tgatgacatc 1380 agaaagcttc tggactcaca aaatagaagg gacataaaac tcattgatgt tgagatgacc 1440 aaagggcct caagagaata tgaagataaa gtgtgggaca aatatggctg gctatgcaaa 1500 atgcacactg gggtagtgag agaaaaaaag aagaaagaga tcaccccaca ctgtgcactc 1560 atggactgca tcatttttga gagtgcttcc aaggcaagac tccctgatct aaaaaccgtt 1620 caacacatcc tgccacatga tttaatcttc agaggaccca atgttgtgac actctaa 1677 <210> 36 <211> 558 <212> PRT <213> Lymphoma virus (mutant P91) <400> 36 Met Ser Leu Ser Lys Glu Val Lys Ser Phe Gln Trp Thr Gln Ala Leu 1 5 10 15 Arg Arg Glu Leu Gln Ser Phe Thr Ser Asp Val Lys Ala Ala Val Ile 20 25 30 Lys Asp Ala Thr Ser Leu Leu Asn Gly Leu Asp Phe Ser Glu Val Ser 35 40 45 Asn Val Gln Arg Ile Met Arg Lys Glu Arg Arg Asp Asp Lys Asp Leu 50 55 60 Gln Arg Leu Arg Ser Leu Asn Gln Thr Val His Ser Leu Val Asp Leu 65 70 75 80 Lys Ser Thr Ser Lys Lys Asn Val Leu Lys Val Gly Arg Leu Ser Ala 85 90 95 Glu Glu Leu Met Thr Leu Ala Ala Asp Leu Glu Lys Leu Lys Ala Lys 100 105 110 Ile Met Arg Thr Glu Arg Pro Gln Ala Ser Gly Val Tyr Met Gly Asn 115 120 125 Leu Thr Ala Gln Gln Leu Asp Gln Arg Ser Gln Ile Leu Gln Met Val 130 135 140 Gly Met Arg Arg Pro Gln Gln Gly Ala Ser Gly Val Val Arg Val Trp 145 150 155 160 Asp Val Lys Asp Ser Ser Leu Leu Asn Asn Gln Phe Gly Thr Met Pro 165 170 175 Ser Leu Thr Met Ala Cys Met Ala Lys Gln Ser Gln Thr Pro Leu Asn 180 185 190 Asp Val Val Gln Ala Leu Thr Asp Leu Gly Leu Leu Tyr Thr Val Lys 195 200 205 Tyr Pro Asn Leu Ser Asp Leu Glu Arg Leu Lys Asp Lys His Pro Val 210 215 220 Leu Gly Val Ile Thr Glu Gln Gln Ser Ser Ile Asn Ile Ser Gly Tyr 225 230 235 240 Asn Phe Ser Leu Gly Ala Ala Val Lys Ala Gly Ala Ala Leu Leu Asp 245 250 255 Gly Gly Asn Met Leu Glu Ser Ile Leu Ile Lys Pro Ser Asn Ser Glu 260 265 270 Asp Leu Leu Lys Ala Val Leu Gly Ala Lys Lys Lys Leu Asn Met Phe 275 280 285 Val Ser Asp Gln Val Gly Asp Arg Asn Pro Tyr Glu Asn Ile Leu Tyr 290 295 300 Lys Val Cys Leu Ser Gly Glu Gly Trp Pro Tyr Ile Ala Cys Arg Thr 305 310 315 320 Ser Val Val Gly Arg Ala Trp Glu Asn Thr Thr Ile Asp Leu Thr Asn 325 330 335 Glu Lys Leu Val Ala Asn Ser Ser Arg Pro Val Pro Gly Ala Ala Gly 340 345 350 Pro Pro Gln Val Gly Leu Ser Tyr Ser Gln Thr Met Leu Leu Lys Asp 355 360 365 Leu Met Gly Gly Ile Asp Pro Asn Ala Pro Thr Trp Ile Asp Ile Glu 370 375 380 Gly Arg Phe Asn Asp Pro Val Glu Ile Ala Ile Phe Gln Pro Gln Asn 385 390 395 400 Gly Gln Phe Ile His Phe Tyr Arg Glu Pro Thr Asp Gln Lys Gln Phe 405 410 415 Lys Gln Asp Ser Lys Tyr Ser His Gly Met Asp Leu Ala Asp Leu Phe 420 425 430 Asn Ala Gln Pro Gly Leu Thr Ser Ser Val Ile Gly Ala Leu Pro Gln 435 440 445 Gly Met Val Leu Ser Cys Gln Gly Ser Asp Asp Ile Arg Lys Leu Leu 450 455 460 Asp Ser Gln Asn Arg Arg Asp Ile Lys Leu Ile Asp Val Glu Met Thr 465 470 475 480 Lys Glu Ala Ser Arg Glu Tyr Glu Asp Lys Val Trp Asp Lys Tyr Gly 485 490 495 Trp Leu Cys Lys Met His Thr Gly Val Val Arg Asp Lys Lys Lys Lys 500 505 510 Glu Ile Thr Pro His Cys Ala Leu Met Asp Cys Ile Ile Phe Glu Ser 515 520 525 Ala Ser Lys Ala Arg Leu Pro Asp Leu Lys Thr Val His Asn Ile Leu 530 535 540 Pro His Asp Leu Ile Phe Arg Gly Pro Asn Val Val Thr Leu 545 550 555 <210> 37 <211> 273 <212> DNA <213> Lymphocytic choriomeningitis virus (mutant P91) <400> 37 atgggccaag gcaagtccaa agaagaaagg gacaccagca atacaggcag agcagagctt 60 ttgccagaca ccacctatct tggtcctcta aattgtaaat catgttggca gaaatttgac 120 agcttggtta gatgccatga ccactatctt tgcagacact gtctgaatct cctgctgtca 180 gtttccgaca gatgtcctct ctgtaagtat ccactgccaa ccaaactgaa ggtgtcaaca 240 gtcccaagct ccccacctcc ctatgaggag tga 273 <210> 38 <211> 90 <212> PRT <213> Lymphocytic choriomeningitis virus (mutant P91) <400> 38 Met Gly Gln Gly Lys Ser Lys Glu Glu Arg Asp Thr Ser Asn Thr Gly 1 5 10 15 Arg Ala Glu Leu Leu Pro Asp Thr Thr Tyr Leu Gly Pro Leu Asn Cys 20 25 30 Lys Ser Cys Trp Gln Lys Phe Asp Ser Leu Val Arg Cys His Asp His 35 40 45 Tyr Leu Cys Arg His Cys Leu Asn Leu Leu Leu Ser Val Ser Asp Arg 50 55 60 Cys Pro Leu Cys Lys Tyr Pro Leu Pro Thr Lys Leu Lys Val Ser Thr 65 70 75 80 Val Pro Ser Ser Pro Pro Pro Tyr Glu Glu 85 90 <210> 39 <211> 6630 <212> DNA <213> Lymphocytic choriomeningitis virus (mutant P91) <400> 39 atggatgaaa ctattgcaga tttgagagag ttgtgtctaa attacataga acaggacgag 60 aggctgtcaa ggcaaaaact caacttcctg ggacaaagag aacccagaat ggtgctaatt 120 gagggactca aattgttatc acgctgtata gagatagaca gtgcagacaa aagtggttgc 180 atacacaacc acgatgacaa atctgttgaa acaatcctaa tagactctgg gattgtgtgt 240 ccaggactgc cactcatcat ccctgatggt tataagttga ttgacaattc ccttattctt 300 cttgaatgtt ttgttagaag cacaccagct agttttgaaa agaagttcat tgaggacacc 360 aacaaactag catgcatcaa agaagatctt gctgttgcag gcatcacact ggttccaata 420 gtggatggtc gttgtgatta tgataacagt ttcatgccag aatgggtgaa ttttaagttc 480 agagacctcc tatttaaact cctggagtat tctagtcaag atgagaaagt ttttgaggag 540 tctgaatact tcaggctctg tgagtctctt aagaccactg ttgacaaacg ttccggcatg 600 gactcaatga aaatttgaa agacgcaaga tcatttcata acgatgagat tatgaaaatg 660 tgccacgatg gtgtcaaccc caacatgagt tgcgatgatg tggtctttgg cataaattcc 720 ttttttggca ggtttaggag ggacctgtta aatgggaaac tcaaaaggaa tttccaaaag 780 gtcagccctg ggggcttaat caaggaattc tctgaacttt atgaaaccct tactgataat 840 gatgacatat taatgttgag caaagaggca gttgaatcct gccccttaat gaggttcatt 900 acagcagaga cccatgggca tgagagagga agcgatgcta acactgagta tgaaaggcta 960 ctctctatgt tgaacaaggt gaaaagttta aaattattaa acactagaag gagacagctg 1020 ctgaacttag atgtcttatg tctttcttca cttattaagc agtcaatttc caaagggttg 1080 gaaaatgata aacattgggt tggttgctgc tacagtagtg tgaatgatag gcttgtgagc 1140 cttcaaagta ccaaagaaga attcatgaga cttttgaaga acagaagaaa atcaagagtg 1200 cacaaaaagg catctcttga tgagcttttt agggtatcca taaatgagtt catagcaaaa 1260 atccagaaat gcctatcaac agtgggactt agttttgagc attacggact atcagaatgc 1320 ctcgtgcaag aatgccatat accatttgct gaatttgaga actttatgag agccgggact 1380 catcctgtaa tgcattacac aaaatttgaa gattacactt tccagcctaa catagagcaa 1440 tgaggtt tacagattt gagaaaactg tcatctgttt gtttggttt aaaaacagc 1500 atgaaaaaaa gctcagttgc aaggttgaga cagaaccaac tgggtctgt gagatatca 1560 gtggtggagt gcaagaggt gttttgccag atataaaac tggattccga agagtatcat 1620 ctactatatc agaaaactgg agaatcatcg aggtgttatt ccatacaagg tccggatggt 1680 cacttgattt ccttttacgc agatccaaaa aggttcttt taccatttt ttcagatgag 1740 gtgttgcaca acatgataga cacaatgatt tcatggatta ggtcatgccc tgacttaaaa 1800 gattctctta ttgacattga gactgcacta aggacattga tcctactgat gctcaccac 1860 Chacaaaga Gaatcaaa GCAggttCA Attattaggt Atttagt ggccatcgtc 1920 tcagacttt catcgacctc attaatggat aagttgaagg aggatctaat cacacctgcc 1980 gagaaagtgg tgtacaggct gcttcggtttt tgattagga caatttttgg tactggtgaa 2040 aaggtgttat tgagtgcaaa attcaagtttt atgttgaatg tgtcatacct gtgtcatttg 2100 atcacaagg agacccctga tagattgaca gatcagataa atgttttga aaagttcttt 2160 gagcccaaga gtgagtttgg tttctttgtc aaccctaagg aaacaatcac acccgaagag 2220 gaatgtgttt tttatgaaca aatgaagaag ttcaccggta aagatattga ttgtcagcat 2280 tcaacccctg gtgttaattt agagatcttt agcatgatgg tatcttcatt caacaatggc 2340 accttaattc taaaagggga gaaaaggctc aacaatctgg accccacatgac caactctgga 2400 tgtgcgacag cattagatct cgcaagcaac aaaagtgtgg ttgtcaataa acatctgaat 2460 ggagaacggc ttttggagta tgattttaac aaattgcttg ttagtgctgt gagccaaatt 2520 acagagggct tcatgaggaa acaaaagtat aagctgagac actcagatta cgaatataag 2580 gtctcaaagc ttgtctctag attagtcatc ggttccagga aaacagaagt agacaaattg 2640 gaagatgatc cggtagatgt gtgtttcgag ggggaggagg agacaagttt tttcaggagt 2700 ttagaagata aggtcagctc cacaataaca cggtataata gaggcactag gcttaatgaa 2760 gggcaagggg agggagaatt caagaacaca aaaggactac accaccttca gattattttg 2820 tcaggtaaaa gagcttatct gaggaaagtc attttatcag aaatttcatt tcatctagta 2880 gaggactttg atccatcctg tctcaccaat gacgacatga ggtttatttg tgaggctgtt 2940 gaaggttcaa cagaactgtc accattgtat tttacatcag ctgtcaaaga acaatgtggt 3000 ctggatgaga tggcaagaaa cctctgtaga aagttcttct cagagggtga ttggttctca 3060 tgtatgaaga tgatcttgtt acagatgaat gcaaatgcgt attcagggaa gtacagacac 3120 atgcagaggc agagcttaaa ttttaaattt gactgggaca aattggaaga agatgtaaga 3180 attagtgaaa gggaaagcaa ttctgaatct ctaagtaagg ccctttcatt gacaaaatgc 3240 atgagtgctg ctctaaagaa tctgtgtttt tactcagaag aatcaccaac atcatacact 3300 tcagttggcc ctgactctgg gagactaaaa tttgcattgt catacaaaga gcaggttggg 3360 ggaatagag agctttacat tggggatttg aggacaaaaa tgttcacaag attggtagaa 3420 gattattttg aatccttttc tagtttctt tcaggatctt gttaaacaa tgataaagag 3480 tttgaaaatg caatcttgtc aatgactatc aatgtgagag aagggttgtt aaactacagc 3540 atggatcaca gcaaatgggg accaatgatg tgcccattcc tattcttaat gcttctccaa 3600 aatctcaaac tgggtgatga tcagtacgtg cgttctggaa aagatcatgt tagcaccttg 3660 ttgacttggc atatgcataa acttgttgaa gtccctttcc ctgttgtgaa tgcaatgatg 3720 aaatcatatg ttaaatcaaa actcaagctt ctcaaagggt caggaacgac tgttacggag 3780 agaatcttta gagagtattt tgaaatgggg gtggtgccat ctcacatatc tagtctcatt 3840 gacatgggac aggggatcct acacaatgct tctgattttt acggtttaat tagtgaaagg 3900 tttatcaatt attgtattgg tgtcattttt ggagagaggc cagaagccta tacatcaagt 3960 gatgatcaga tcactttatt tgacaagaga ttgagtgact tagttgatag tgacccagaa 4020 gaagtccttg tcttgctgga attccactct cacttaagtg gtttgttgaa caagttcatc 4080 agtccaaaaa gtgtggttgg gcggtttgca gcggaattca aatccagatt ttatgtgtgg 4140 ggggaggagg tccctctcct cacgaaattt gtgtctgcgg cactacacaa tgttaagtgt 4200 aaagaaccgc atcaactttg tgagacaata gatacgattg ctgatcaagc tatagcaaat 4260 ggagttccag tttttttagt aaactgtatc cagaggagga cactggatct cttgaaatat 4320 gctaatttcc ctttagatcc attcttgtta aacactcaca ctgatgtaaa ggattggtta 4380 gatggttcta gaggttatag atccaaga ctcattgaag aattgtgtcc cagtgaaaca 4440 aagatcatga gaaacttgt aagaacta catcacaac tcagaacgg tgaatgtaac 4500 gaggaatttt ttcagacct cttcacagg gaaaggaag aggcatcct tcattggga 4560 gagattcttg gtcttgagga tgatcttaat gagttggcaa gcatcattg gttgaatctg 4620 aatgaaatgt tcccattgag gatggttctg agacaaaag tggtttaccc atcagtaatg 4680 accttcaag aggaaagat cccctcattg attaaaacc tccaaaataa gctttgtagt 4740 aagttcaca gaggtgcaca gaagctgttg tcagaggcaa tcaaatc agcttttcag 4800 agttgtgtct catccggctt tataggtctc tgtaagactt taggagtag gtgtgtgaga 4860 aaaaaaaca gggaaaatat gtatatcaga aaggtgcttg aagatctgac catggatgaa 4920 catgtcaca gggttcacaa acatttgt gtgatgttgt acatttgcga caacagaga 4980 cacccagagg ctcaccgtga ccacatcaac ctttgaggc cccttctctg ggactacatt 5040 tgcatctcat tgagcaactc ttttgagctg ggtgtttggg ttttagcaga acctgtgaaa 5100 ggaaagaacg agagtaattc ggctgttagg cacttaaatc catgtgatta tgtagcaaga 5160 aaacctgaga gttcgagact actagaggat aaagtgagtt tgaatcatgt aattcaatct 5220 gtgaggcgac tgtaccccaa aatctttgag gatcagttgc tcccattcat gtctgatgtg 5280 agctcaaaaa atatgagatg gagtcccagg attaaattcc ttgacctttg tgtgctgatt 5340 gacatcaact cagagtcttt gtcactcatt tctcatgttg tcaaatggaa gagggacgaa 5400 cattacactg tgctgttttc tgatctcgtc aactctcacc aacggtcaga ctcaagttta 5460 gttgatgaat ttgttgtcag cacaagggat gtctgcaaga actttttgaa gcaagtgtat 5520 ttcgaatcat ttgtacgaga gtttgttgca acagctagga ccttaggtaa cttttcatgg 5580 ttcccccata aggacatgat gccatctgaa gatggcgctg aagcactggg acccttccaa 5640 tcatttattt tgaaagtggt gaacaagaaa atagagaggc ccatgtttag gaatgacttg 5700 cagtttggtt ttggttggtt ctcttatcgt gtgggggatg ttgtgtgtaa tgccgctatg 5760 ttaattaagc agggtttgac agatccaaaa gcatttaaat ctttaagaga tttgtgggat 5820 tacatgctca gcagcacaga ggggatattg gagttctcaa tcacagtgga tttcacacac 5880 aaccagaaca acactgactg cttgaggaaa ttttcattga tctttgtggt taaatgccaa 5940 ttacagagtc caggtgtagc tgattactta tcgtgctctc attccttcaa aggtgaggtt 6000 gacaggagat tattagatga gtgtctcaat ctgttgagga cagaccccat ctttaaagcg 6060 aatgatggag tctttgacat taggtctgaa gagtttgaag attacatgga agaccctttg 6120 acacttggtg attcactaga acttgaacta ataggttcta gaaggattct gaatgagatc 6180 aaatctactg actttgagag gatagggcct gagtgggaac ctgtgcctct gaccataagg 6240 aagggtgccc tctttgaggg gaggaacttt gttcagaata tctctgtgaa attggagaca 6300 aaggacatga gggtctttct ggcagagctc gagggctgtg gaaaaattgg tgatgtcctc 6360 ggcagcctcc tcctgcaccg attcagaact ggtgagcact tgatggagtc agaaataagt 6420 acagttcttc aggagctctg catggacaga tccgtcatgc tgacaccatt atcttttgtg 6480 ccagattggt tcaccttcag agattgtagg ctctgcttca gcargtcaaa gaacactgta 6540 atgtatgaga caactggggg caggttcaga ctcaagggga aatcctgtga cgattggctg 6600 gcggagcggg tggccgagga gatcgactag 6630 <210> 40 <211> 2209 <212> PRT <213> Lymphocytic choriomeningitis virus (mutant P91) <220> <221> MISC_FEATURE <222> (2175)..(2175) <223> Xaa can be Arg or Lys <400> 40 Met Asp Glu Thr Ile Ala Asp Leu Arg Glu Leu Cys Leu Asn Tyr Ile 1 5 10 15 Glu Gln Asp Glu Arg Leu Ser Arg Gln Lys Leu Asn Phe Leu Gly Gln 20 25 30 Arg Glu Pro Arg Met Val Leu Ile Glu Gly Leu Lys Leu Leu Ser Arg 35 40 45 Cys Ile Glu Ile Asp Ser Ala Asp Lys Ser Gly Cys Ile His Asn His 50 55 60 Asp Asp Lys Ser Val Glu Thr Ile Leu Ile Asp Ser Gly Ile Val Cys 65 70 75 80 Pro Gly Leu Pro Leu Ile Ile Pro Asp Gly Tyr Lys Leu Ile Asp Asn 85 90 95 Ser Leu Ile Leu Leu Glu Cys Phe Val Arg Ser Thr Pro Ala Ser Phe 100 105 110 Glu Lys Lys Phe Ile Glu Asp Thr Asn Lys Leu Ala Cys Ile Lys Glu 115 120 125 Asp Leu Ala Val Ala Gly Ile Thr Leu Val Pro Ile Val Asp Gly Arg 130 135 140 Cys Asp Tyr Asp Asn Ser Phe Met Pro Glu Trp Val Asn Phe Lys Phe 145 150 155 160 Arg Asp Leu Leu Phe Lys Leu Leu Glu Tyr Ser Ser Gln Asp Glu Lys 165 170 175 Val Phe Glu Glu Ser Glu Tyr Phe Arg Leu Cys Glu Ser Leu Lys Thr 180 185 190 Thr Val Asp Lys Arg Ser Gly Met Asp Ser Met Lys Ile Leu Lys Asp 195 200 205 Ala Arg Ser Phe His Asn Asp Glu Ile Met Lys Met Cys His Asp Gly 210 215 220 Val Asn Pro Asn Met Ser Cys Asp Asp Val Val Phe Gly Ile Asn Ser 225 230 235 240 Phe Phe Gly Arg Phe Arg Arg Asp Leu Leu Asn Gly Lys Leu Lys Arg 245 250 255 Asn Phe Gln Lys Val Ser Pro Gly Gly Leu Ile Lys Glu Phe Ser Glu 260 265 270 Leu Tyr Glu Thr Leu Thr Asp Asn Asp Asp Ile Leu Met Leu Ser Lys 275 280 285 Glu Ala Val Glu Ser Cys Pro Leu Met Arg Phe Ile Thr Ala Glu Thr 290 295 300 His Gly His Glu Arg Gly Ser Asp Ala Asn Thr Glu Tyr Glu Arg Leu 305 310 315 320 Leu Ser Met Leu Asn Lys Val Lys Ser Leu Lys Leu Leu Asn Thr Arg 325 330 335 Arg Arg Gln Leu Leu Asn Leu Asp Val Leu Cys Leu Ser Ser Leu Ile 340 345 350 Lys Gln Ser Ile Ser Lys Gly Leu Glu Asn Asp Lys His Trp Val Gly 355 360 365 Cys Cys Tyr Ser Ser Val Asn Asp Arg Leu Val Ser Leu Gln Ser Thr 370 375 380 Lys Glu Glu Phe Met Arg Leu Leu Lys Asn Arg Arg Lys Ser Arg Val 385 390 395 400 His Lys Lys Ala Ser Leu Asp Glu Leu Phe Arg Val Ser Ile Asn Glu 405 410 415 Phe Ile Ala Lys Ile Gln Lys Cys Leu Ser Thr Val Gly Leu Ser Phe 420 425 430 Glu His Tyr Gly Leu Ser Glu Cys Leu Val Gln Glu Cys His Ile Pro 435 440 445 Phe Ala Glu Phe Glu Asn Phe Met Arg Ala Gly Thr His Pro Val Met 450 455 460 His Tyr Thr Lys Phe Glu Asp Tyr Thr Phe Gln Pro Asn Ile Glu Gln 465 470 475 480 Leu Arg Gly Leu Gln Ser Leu Arg Lys Leu Ser Ser Val Cys Leu Ala 485 490 495 Leu Thr Asn Ser Met Lys Thr Ser Ser Val Ala Arg Leu Arg Gln Asn 500 505 510 Gln Leu Gly Ser Val Arg Tyr Gln Val Val Glu Cys Lys Glu Val Phe 515 520 525 Cys Gln Ile Ile Lys Leu Asp Ser Glu Glu Tyr His Leu Leu Tyr Gln 530 535 540 Lys Thr Gly Glu Ser Ser Arg Cys Tyr Ser Ile Gln Gly Pro Asp Gly 545 550 555 560 His Leu Ile Ser Phe Tyr Ala Asp Pro Lys Arg Phe Phe Leu Pro Ile 565 570 575 Phe Ser Asp Glu Val Leu His Asn Met Ile Asp Thr Met Ile Ser Trp 580 585 590 Ile Arg Ser Cys Pro Asp Leu Lys Asp Ser Leu Ile Asp Ile Glu Thr 595 600 605 Ala Leu Arg Thr Leu Ile Leu Leu Met Leu Thr Asn Pro Thr Lys Arg 610 615 620 Asn Gln Lys Gln Val Gln Asn Ile Arg Tyr Leu Val Met Ala Ile Val 625 630 635 640 Ser Asp Phe Ser Ser Thr Ser Leu Met Asp Lys Leu Lys Glu Asp Leu 645 650 655 Ile Thr Pro Ala Glu Lys Val Val Tyr Arg Leu Leu Arg Phe Leu Ile 660 665 670 Arg Thr Ile Phe Gly Thr Gly Glu Lys Val Leu Leu Ser Ala Lys Phe 675 680 685 Lys Phe Met Leu Asn Val Ser Tyr Leu Cys His Leu Ile Thr Lys Glu 690 695 700 Thr Pro Asp Arg Leu Thr Asp Gln Ile Lys Cys Phe Glu Lys Phe Phe 705 710 715 720 Glu Pro Lys Ser Glu Phe Gly Phe Phe Val Asn Pro Lys Glu Thr Ile 725 730 735 Thr Pro Glu Glu Glu Cys Val Phe Tyr Glu Gln Met Lys Lys Phe Thr 740 745 750 Gly Lys Asp Ile Asp Cys Gln His Ser Thr Pro Gly Val Asn Leu Glu 755 760 765 Ile Phe Ser Met Met Val Ser Ser Phe Asn Asn Gly Thr Leu Ile Leu 770 775 780 Lys Gly Glu Lys Arg Leu Asn Asn Leu Asp Pro Met Thr Asn Ser Gly 785 790 795 800 Cys Ala Thr Ala Leu Asp Leu Ala Ser Asn Lys Ser Val Val Val Asn 805 810 815 Lys His Leu Asn Gly Glu Arg Leu Leu Glu Tyr Asp Phe Asn Lys Leu 820 825 830 Leu Val Ser Ala Val Ser Gln Ile Thr Glu Gly Phe Met Arg Lys Gln 835 840 845 Lys Tyr Lys Leu Arg His Ser Asp Tyr Glu Tyr Lys Val Ser Lys Leu 850 855 860 Val Ser Arg Leu Val Ile Gly Ser Arg Lys Thr Glu Val Asp Lys Leu 865 870 875 880 Glu Asp Asp Pro Val Asp Val Cys Phe Glu Gly Glu Glu Glu Thr Ser 885 890 895 Phe Phe Arg Ser Leu Glu Asp Lys Val Ser Ser Thr Ile Thr Arg Tyr 900 905 910 Asn Arg Gly Thr Arg Leu Asn Glu Gly Gln Gly Glu Gly Glu Phe Lys 915 920 925 Asn Thr Lys Gly Leu His His Leu Gln Ile Ile Leu Ser Gly Lys Arg 930 935 940 Ala Tyr Leu Arg Lys Val Ile Leu Ser Glu Ile Ser Phe His Leu Val 945 950 955 960 Glu Asp Phe Asp Pro Ser Cys Leu Thr Asn Asp Asp Met Arg Phe Ile 965 970 975 Cys Glu Ala Val Glu Gly Ser Thr Glu Leu Ser Pro Leu Tyr Phe Thr 980 985 990 Ser Ala Val Lys Glu Gln Cys Gly Leu Asp Glu Met Ala Arg Asn Leu 995 1000 1005 Cys Arg Lys Phe Phe Ser Glu Gly Asp Trp Phe Ser Cys Met Lys 1010 1015 1020 Met Ile Leu Leu Gln Met Asn Ala Asn Ala Tyr Ser Gly Lys Tyr 1025 1030 1035 Arg His Met Gln Arg Gln Ser Leu Asn Phe Lys Phe Asp Trp Asp 1040 1045 1050 Lys Leu Glu Glu Asp Val Arg Ile Ser Glu Arg Glu Ser Asn Ser 1055 1060 1065 Glu Ser Leu Ser Lys Ala Leu Ser Leu Thr Lys Cys Met Ser Ala 1070 1075 1080 Ala Leu Lys Asn Leu Cys Phe Tyr Ser Glu Glu Ser Pro Thr Ser 1085 1090 1095 Tyr Thr Ser Val Gly Pro Asp Ser Gly Arg Leu Lys Phe Ala Leu 1100 1105 1110 Ser Tyr Lys Glu Gln Val Gly Gly Asn Arg Glu Leu Tyr Ile Gly 1115 1120 1125 Asp Leu Arg Thr Lys Met Phe Thr Arg Leu Val Glu Asp Tyr Phe 1130 1135 1140 Glu Ser Phe Ser Ser Phe Phe Ser Gly Ser Cys Leu Asn Asn Asp 1145 1150 1155 Lys Glu Phe Glu Asn Ala Ile Leu Ser Met Thr Ile Asn Val Arg 1160 1165 1170 Glu Gly Leu Leu Asn Tyr Ser Met Asp His Ser Lys Trp Gly Pro 1175 1180 1185 Met Met Cys Pro Phe Leu Phe Leu Met Leu Leu Gln Asn Leu Lys 1190 1195 1200 Leu Gly Asp Asp Gln Tyr Val Arg Ser Gly Lys Asp His Val Ser 1205 1210 1215 Thr Leu Leu Thr Trp His Met His Lys Leu Val Glu Val Pro Phe 1220 1225 1230 Pro Val Val Asn Ala Met Met Lys Ser Tyr Val Lys Ser Lys Leu 1235 1240 1245 Lys Leu Leu Lys Gly Ser Gly Thr Thr Val Thr Glu Arg Ile Phe 1250 1255 1260 Arg Glu Tyr Phe Glu Met Gly Val Val Pro Ser His Ile Ser Ser 1265 1270 1275 Leu Ile Asp Met Gly Gln Gly Ile Leu His Asn Ala Ser Asp Phe 1280 1285 1290 Tyr Gly Leu Ile Ser Glu Arg Phe Ile Asn Tyr Cys Ile Gly Val 1295 1300 1305 Ile Phe Gly Glu Arg Pro Glu Ala Tyr Thr Ser Ser Asp Asp Gln 1310 1315 1320 Ile Thr Leu Phe Asp Lys Arg Leu Ser Asp Leu Val Asp Ser Asp 1325 1330 1335 Pro Glu Glu Val Leu Val Leu Leu Glu Phe His Ser His Leu Ser 1340 1345 1350 Gly Leu Leu Asn Lys Phe Ile Ser Pro Lys Ser Val Val Gly Arg 1355 1360 1365 Phe Ala Ala Glu Phe Lys Ser Arg Phe Tyr Val Trp Gly Glu Glu 1370 1375 1380 Val Pro Leu Leu Thr Lys Phe Val Ser Ala Ala Leu His Asn Val 1385 1390 1395 Lys Cys Lys Glu Pro His Gln Leu Cys Glu Thr Ile Asp Thr Ile 1400 1405 1410 Ala Asp Gln Ala Ile Ala Asn Gly Val Pro Val Phe Leu Val Asn 1415 1420 1425 Cys Ile Gln Arg Arg Thr Leu Asp Leu Leu Lys Tyr Ala Asn Phe 1430 1435 1440 Pro Leu Asp Pro Phe Leu Leu Asn Thr His Thr Asp Val Lys Asp 1445 1450 1455 Trp Leu Asp Gly Ser Arg Gly Tyr Arg Ile Gln Arg Leu Ile Glu 1460 1465 1470 Glu Leu Cys Pro Ser Glu Thr Lys Ile Met Arg Lys Leu Val Arg 1475 1480 1485 Arg Leu His His Lys Leu Lys Asn Gly Glu Cys Asn Glu Glu Phe 1490 1495 1500 Phe Leu Asp Leu Phe Asn Arg Glu Lys Glu Glu Ala Ile Leu Gln 1505 1510 1515 Leu Gly Glu Ile Leu Gly Leu Glu Asp Asp Leu Asn Glu Leu Ala 1520 1525 1530 Ser Ile Asn Trp Leu Asn Leu Asn Glu Met Phe Pro Leu Arg Met 1535 1540 1545 Val Leu Arg Gln Lys Val Val Tyr Pro Ser Val Met Thr Phe Gln 1550 1555 1560 Glu Glu Lys Ile Pro Ser Leu Ile Lys Thr Leu Gln Asn Lys Leu 1565 1570 1575 Cys Ser Lys Phe Thr Arg Gly Ala Gln Lys Leu Leu Ser Glu Ala 1580 1585 1590 Ile Asn Lys Ser Ala Phe Gln Ser Cys Val Ser Ser Gly Phe Ile 1595 1600 1605 Gly Leu Cys Lys Thr Leu Gly Ser Arg Cys Val Arg Asn Lys Asn 1610 1615 1620 Arg Glu Asn Met Tyr Ile Arg Lys Val Leu Glu Asp Leu Thr Met 1625 1630 1635 Asp Glu His Val Thr Arg Val His Lys Gln Asp Gly Val Met Leu 1640 1645 1650 Tyr Ile Cys Asp Lys Gln Arg His Pro Glu Ala His Arg Asp His 1655 1660 1665 Ile Asn Leu Leu Arg Pro Leu Leu Trp Asp Tyr Ile Cys Ile Ser 1670 1675 1680 Leu Ser Asn Ser Phe Glu Leu Gly Val Trp Val Leu Ala Glu Pro 1685 1690 1695 Val Lys Gly Lys Asn Glu Ser Asn Ser Ala Val Arg His Leu Asn 1700 1705 1710 Pro Cys Asp Tyr Val Ala Arg Lys Pro Glu Ser Ser Arg Leu Leu 1715 1720 1725 Glu Asp Lys Val Ser Leu Asn His Val Ile Gln Ser Val Arg Arg 1730 1735 1740 Leu Tyr Pro Lys Ile Phe Glu Asp Gln Leu Leu Pro Phe Met Ser 1745 1750 1755 Asp Val Ser Ser Lys Asn Met Arg Trp Ser Pro Arg Ile Lys Phe 1760 1765 1770 Leu Asp Leu Cys Val Leu Ile Asp Ile Asn Ser Glu Ser Leu Ser 1775 1780 1785 Leu Ile Ser His Val Val Lys Trp Lys Arg Asp Glu His Tyr Thr 1790 1795 1800 Val Leu Phe Ser Asp Leu Val Asn Ser His Gln Arg Ser Asp Ser 1805 1810 1815 Ser Leu Val Asp Glu Phe Val Val Ser Thr Arg Asp Val Cys Lys 1820 1825 1830 Asn Phe Leu Lys Gln Val Tyr Phe Glu Ser Phe Val Arg Glu Phe 1835 1840 1845 Val Ala Thr Ala Arg Thr Leu Gly Asn Phe Ser Trp Phe Pro His 1850 1855 1860 Lys Asp Met Met Pro Ser Glu Asp Gly Ala Glu Ala Leu Gly Pro 1865 1870 1875 Phe Gln Ser Phe Ile Leu Lys Val Val Asn Lys Lys Ile Glu Arg 1880 1885 1890 Pro Met Phe Arg Asn Asp Leu Gln Phe Gly Phe Gly Trp Phe Ser 1895 1900 1905 Tyr Arg Val Gly Asp Val Val Cys Asn Ala Ala Met Leu Ile Lys 1910 1915 1920 Gln Gly Leu Thr Asp Pro Lys Ala Phe Lys Ser Leu Arg Asp Leu 1925 1930 1935 Trp Asp Tyr Met Leu Ser Ser Thr Glu Gly Ile Leu Glu Phe Ser 1940 1945 1950 Ile Thr Val Asp Phe Thr His Asn Gln Asn Asn Thr Asp Cys Leu 1955 1960 1965 Arg Lys Phe Ser Leu Ile Phe Val Val Lys Cys Gln Leu Gln Ser 1970 1975 1980 Pro Gly Val Ala Asp Tyr Leu Ser Cys Ser His Ser Phe Lys Gly 1985 1990 1995 Glu Val Asp Arg Arg Leu Leu Asp Glu Cys Leu Asn Leu Leu Arg 2000 2005 2010 Thr Asp Pro Ile Phe Lys Ala Asn Asp Gly Val Phe Asp Ile Arg 2015 2020 2025 Ser Glu Glu Phe Glu Asp Tyr Met Glu Asp Pro Leu Thr Leu Gly 2030 2035 2040 Asp Ser Leu Glu Leu Glu Leu Ile Gly Ser Arg Arg Ile Leu Asn 2045 2050 2055 Glu Ile Lys Ser Thr Asp Phe Glu Arg Ile Gly Pro Glu Trp Glu 2060 2065 2070 Pro Val Pro Leu Thr Ile Arg Lys Gly Ala Leu Phe Glu Gly Arg 2075 2080 2085 Asn Phe Val Gln Asn Ile Ser Val Lys Leu Glu Thr Lys Asp Met 2090 2095 2100 Arg Val Phe Leu Ala Glu Leu Glu Gly Cys Gly Lys Ile Gly Asp 2105 2110 2115 Val Leu Gly Ser Leu Leu Leu His Arg Phe Arg Thr Gly Glu His 2120 2125 2130 Leu Met Glu Ser Glu Ile Ser Thr Val Leu Gln Glu Leu Cys Met 2135 2140 2145 Asp Arg Ser Val Met Leu Thr Pro Leu Ser Phe Val Pro Asp Trp 2150 2155 2160 Phe Thr Phe Arg Asp Cys Arg Leu Cys Phe Ser Xaa Ser Lys Asn 2165 2170 2175 Thr Val Met Tyr Glu Thr Thr Gly Gly Arg Phe Arg Leu Lys Gly 2180 2185 2190 Lys Ser Cys Asp Asp Trp Leu Ala Glu Arg Val Ala Glu Glu Ile 2195 2200 2205 Asp <210> 41 <211> 1497 <212> DNA <213> Lymphocytic choriomeningitis virus (mutant P52-1) <400> 41 atgggtcaga ttgtgacaat gtttgaggct ttgcctcaca tcattgatga ggtcatcaac 60 attgtcatta ttgtgctcat tataatcacg agcatcaaag ctgtgtacaa tttcgccacc 120 tgtgggatat tagcactggt cagcttcctt tttttggctg gtaggtcctg tggcatgtac 180 ggcctcaatg gtcccgacat ctataaaggg gtttaccagt tcaaatcagt ggagtttgat 240 atgtctcact taaatctgac gatgcccaat gcgtgctcag ccaacaactc tcatcactac 300 atcagtatgg gaagctctgg actggagcta actttcacta acgactccat ccttaatcac 360 aatttttgca acttaacctc cgctttcaac aaaaagactt ttgaccatac actcatgagt 420 atagtctcga gtctgcacct cagtattaga gggaattcca accacaaagc agtgtcttgt 480 gattttaaca atggcatcac cattcaatac aacttgtcat tttcggaccc acagagcgct 540 atgagccagt gttggacttt cagaggtaga gtcttggaca tgtttagaac tgcctttgga 600 ggaaaataca tgagaagtgg ctggggctgg gcaggttcag atggcaagac cacttggtgc 660 agccaaacaa gctatcagta cctaatcata caaaacagga cttgggaaaa ccactgtaga 720 tatgcaggcc cttttgggat gtctagaatc ctctttgctc aggaaaagac aaagtttctc 780 actaggagac ttgcaggcac attcacctgg accctgtcag actcctcagg agtagaaaat 840 ccaggtggtt attgcctgac caaatggatg atccttgctg cagagctcaa atgttttggg 900 aatacagctg ttgcaaaatg taatgtcaat catgatgaag agttctgtga catgctacga 960 ctaattgatt acaacaaggc cgccctgagt aagttcaagc aagatgtaga gtctgccttg 1020 catgtattca aaacaacagt aaattcttg atttccgatc agctgttgat gaggaatcat 1080 ctaagagatc taatgggggt accatactgt aattactcaa agttctggta tctggaacat 1140 gctaagactg gtgagactag tgtacccaag tgctggcttg tcactaatg ctcctacttg 1200 aatgagaccc actttagtga tcaaatcgaa caagaagcag ataacatgat cacagagatg 1260 ttgaggaagg actacataaa aagacaaggg agtactcctt tagccttaat ggatctttttg 1320 atgttttcaa catcagcata tctaatcagc atctttctgc atcttgtgaa gataccaaca 1380 catagacaca taaagggcgg ttcatgtcca aagccacaccc gcttgaccaa caaggggatc 1440 tgtagttgtg gtgcattcaa ggtgcctggt gtaaaaacta tctggaaaag acgctga 1497 <210> 42 <211> 498 <212> PRT <213> Lymphocytic choriomeningitis virus (mutant P52-1) <400> 42 Met Gly Gln Ile Val Thr Met Phe Glu Ala Leu Pro His Ile Ile Asp 1 5 10 15 Glu Val Ile Asn Ile Val Ile Ile Val Leu Ile Ile Ile Thr Ser Ile 20 25 30 Lys Ala Val Tyr Asn Phe Ala Thr Cys Gly Ile Leu Ala Leu Val Ser 35 40 45 Phe Leu Phe Leu Ala Gly Arg Ser Cys Gly Met Tyr Gly Leu Asn Gly 50 55 60 Pro Asp Ile Tyr Lys Gly Val Tyr Gln Phe Lys Ser Val Glu Phe Asp 65 70 75 80 Met Ser His Leu Asn Leu Thr Met Pro Asn Ala Cys Ser Ala Asn Asn 85 90 95 Ser His His Tyr Ile Ser Met Gly Ser Ser Gly Leu Glu Leu Thr Phe 100 105 110 Thr Asn Asp Ser Ile Leu Asn His Asn Phe Cys Asn Leu Thr Ser Ala 115 120 125 Phe Asn Lys Lys Thr Phe Asp His Thr Leu Met Ser Ile Val Ser Ser 130 135 140 Leu His Leu Ser Ile Arg Gly Asn Ser Asn His Lys Ala Val Ser Cys 145 150 155 160 Asp Phe Asn Asn Gly Ile Thr Ile Gln Tyr Asn Leu Ser Phe Ser Asp 165 170 175 Pro Gln Ser Ala Met Ser Gln Cys Trp Thr Phe Arg Gly Arg Val Leu 180 185 190 Asp Met Phe Arg Thr Ala Phe Gly Gly Lys Tyr Met Arg Ser Gly Trp 195 200 205 Gly Trp Ala Gly Ser Asp Gly Lys Thr Thr Trp Cys Ser Gln Thr Ser 210 215 220 Tyr Gln Tyr Leu Ile Ile Gln Asn Arg Thr Trp Glu Asn His Cys Arg 225 230 235 240 Tyr Ala Gly Pro Phe Gly Met Ser Arg Ile Leu Phe Ala Gln Glu Lys 245 250 255 Thr Lys Phe Leu Thr Arg Arg Leu Ala Gly Thr Phe Thr Trp Thr Leu 260 265 270 Ser Asp Ser Ser Gly Val Glu Asn Pro Gly Gly Tyr Cys Leu Thr Lys 275 280 285 Trp Met Ile Leu Ala Ala Glu Leu Lys Cys Phe Gly Asn Thr Ala Val 290 295 300 Ala Lys Cys Asn Val Asn His Asp Glu Glu Phe Cys Asp Met Leu Arg 305 310 315 320 Leu Ile Asp Tyr Asn Lys Ala Ala Leu Ser Lys Phe Lys Gln Asp Val 325 330 335 Glu Ser Ala Leu His Val Phe Lys Thr Thr Val Asn Ser Leu Ile Ser 340 345 350 Asp Gln Leu Leu Met Arg Asn His Leu Arg Asp Leu Met Gly Val Pro 355 360 365 Tyr Cys Asn Tyr Ser Lys Phe Trp Tyr Leu Glu His Ala Lys Thr Gly 370 375 380 Glu Thr Ser Val Pro Lys Cys Trp Leu Val Thr Asn Gly Ser Tyr Leu 385 390 395 400 Asn Glu Thr His Phe Ser Asp Gln Ile Glu Gln Glu Ala Asp Asn Met 405 410 415 Ile Thr Glu Met Leu Arg Lys Asp Tyr Ile Lys Arg Gln Gly Ser Thr 420 425 430 Pro Leu Ala Leu Met Asp Leu Leu Met Phe Ser Thr Ser Ala Tyr Leu 435 440 445 Ile Ser Ile Phe Leu His Leu Val Lys Ile Pro Thr His Arg His Ile 450 455 460 Lys Gly Gly Ser Cys Pro Lys Pro His Arg Leu Thr Asn Lys Gly Ile 465 470 475 480 Cys Ser Cys Gly Ala Phe Lys Val Pro Gly Val Lys Thr Ile Trp Lys 485 490 495 Arg Arg <210> 43 <211> 1677 <212> DNA <213> Lymphocytic choriomeningitis virus (mutant P52-1) <400> 43 atgtctttgt ccaaagaagt caaaagcttt cagtggacac aggcgttgag gagggagttg 60 cagagtttta catcagatgt aaaggctgcc gtcatcaagg acgcaaccag tcttctaaat 120 gggttggact tttctgaagt cagcaacgtt cagaggatca tgagaaagga aaggagggat 180 gataaagact tgcagagact caggagtctt aaccagactg tgcattctct tgttgatctg 240 aagtctacat caaagaaaaa tgttctgaaa gtgggaagac ttagtgcaga ggaattgatg 300 acccttgcag ctgatcttga gaagctgaag gccaaaatta tgagaactga gaggcctcaa 360 gcttctggag tctacatggg aaatttgaca gcacaacaac ttgatcaaag atcccaaata 420 ctgcaaatgg ttgggatgag aagacctcag cagggtgcaa gtggtgtagt aagggttttgg 480 gatgtgaagg actcatcact tctgaacaat cagttcggca caatgccaag cctgacaatg 540 gcttgcatgg caaaacgtc acagacccca ctcaatgatg ttgtgcaggc actcacagac 600 cttggcttac tttacacagt caaatacccg aatctcagtg atcttgaaag gctaaaggat 660 aaacacccag ttctgggggt cattactgaa cagcaatcta gtatcaatat ctctggttat 720 aatttcagtc ttggtgcagc tgtgaaagcg ggggcagctc tgctagatgg agggaacatg 780 ctggaatcta tcttgatcaa accgagcaac agtgaggatc tcctaaaagc agtctcggg 840 gccaagaaga aactcaacat gtttgtctca gatcaagttg gagatagaaa tccctatgaa 900 aacatccttt ataaagtctg tctttcaggt gaaggatggc catacatagc ctgtagaacg 960 tcagttgtgg ggagagcatg ggagaacaca acaattgatc tcacaaatga aaaacttgtt 1020 gccaactcat ctaggccagt gcctggagca gcaggccac ctcaggtggg cttgagttac 1080 agtcagacaa tgctgttgaa agacttg ggaggttg atcccaatgc tcccacatgg 1140 attgacattg agggcaggtt caatgatcca gtggagatag caatattcca accacaaat 1200 gggcaattca tacatttta caggacct aggaccaga agcaatca gcaggactca 1260 aagtattcac acggcatgga tctgctgat ctctcaatg cacagcctgg gctgacctca 1320 tcagttatag gtgctctccc acagggatg gtttgagct gtcaggttc tgatgacatc 1380 agaaagcttc tggactcaca aaatagaagg gataaaac tcattgatgt tgagatgacc 1440 aaggaggcct caagagaata tgaagaataa gtgtgggaca atatggctg gctatgcaaa 1500 atgcacactg gggtagtgag agacaaaag aagaaagaga tcacccaca ctgtgcactc 1560 atggactgca tcattttga gagtgcttcc aaggcaagac tccctctt aaaaaccgtt 1620 cacacatcc tgccacatga attaatctc agaggaccca atgttgtgac actctaa 1677 <210> 44 <211> 558 <212> PRT <213> Lymphoma virus (mutant P52-1) <400> 44 Met Ser Leu Ser Lys Glu Val Lys Ser Phe Gln Trp Thr Gln Ala Leu 1 5 10 15 Arg Arg Glu Leu Gln Ser Phe Thr Ser Asp Val Lys Ala Ala Val Ile 20 25 30 Lys Asp Ala Thr Ser Leu Leu Asn Gly Leu Asp Phe Ser Glu Val Ser 35 40 45 Asn Val Gln Arg Ile Met Arg Lys Glu Arg Arg Asp Asp Lys Asp Leu 50 55 60 Gln Arg Leu Arg Ser Leu Asn Gln Thr Val His Ser Leu Val Asp Leu 65 70 75 80 Lys Ser Thr Ser Lys Lys Asn Val Leu Lys Val Gly Arg Leu Ser Ala 85 90 95 Glu Glu Leu Met Thr Leu Ala Ala Asp Leu Glu Lys Leu Lys Ala Lys 100 105 110 Ile Met Arg Thr Glu Arg Pro Gln Ala Ser Gly Val Tyr Met Gly Asn 115 120 125 Leu Thr Ala Gln Gln Leu Asp Gln Arg Ser Gln Ile Leu Gln Met Val 130 135 140 Gly Met Arg Arg Pro Gln Gln Gly Ala Ser Gly Val Val Arg Val Trp 145 150 155 160 Asp Val Lys Asp Ser Ser Leu Leu Asn Asn Gln Phe Gly Thr Met Pro 165 170 175 Ser Leu Thr Met Ala Cys Met Ala Lys Gln Ser Gln Thr Pro Leu Asn 180 185 190 Asp Val Val Gln Ala Leu Thr Asp Leu Gly Leu Leu Tyr Thr Val Lys 195 200 205 Tyr Pro Asn Leu Ser Asp Leu Glu Arg Leu Lys Asp Lys His Pro Val 210 215 220 Leu Gly Val Ile Thr Glu Gln Gln Ser Ser Ile Asn Ile Ser Gly Tyr 225 230 235 240 Asn Phe Ser Leu Gly Ala Ala Val Lys Ala Gly Ala Ala Leu Leu Asp 245 250 255 Gly Gly Asn Met Leu Glu Ser Ile Leu Ile Lys Pro Ser Asn Ser Glu 260 265 270 Asp Leu Leu Lys Ala Val Leu Gly Ala Lys Lys Lys Leu Asn Met Phe 275 280 285 Val Ser Asp Gln Val Gly Asp Arg Asn Pro Tyr Glu Asn Ile Leu Tyr 290 295 300 Lys Val Cys Leu Ser Gly Glu Gly Trp Pro Tyr Ile Ala Cys Arg Thr 305 310 315 320 Ser Val Val Gly Arg Ala Trp Glu Asn Thr Thr Ile Asp Leu Thr Asn 325 330 335 Glu Lys Leu Val Ala Asn Ser Ser Arg Pro Val Pro Gly Ala Ala Gly 340 345 350 Pro Pro Gln Val Gly Leu Ser Tyr Ser Gln Thr Met Leu Leu Lys Asp 355 360 365 Leu Met Gly Gly Ile Asp Pro Asn Ala Pro Thr Trp Ile Asp Ile Glu 370 375 380 Gly Arg Phe Asn Asp Pro Val Glu Ile Ala Ile Phe Gln Pro Gln Asn 385 390 395 400 Gly Gln Phe Ile His Phe Tyr Arg Glu Pro Thr Asp Gln Lys Gln Phe 405 410 415 Lys Gln Asp Ser Lys Tyr Ser His Gly Met Asp Leu Ala Asp Leu Phe 420 425 430 Asn Ala Gln Pro Gly Leu Thr Ser Ser Val Ile Gly Ala Leu Pro Gln 435 440 445 Gly Met Val Leu Ser Cys Gln Gly Ser Asp Asp Ile Arg Lys Leu Leu 450 455 460 Asp Ser Gln Asn Arg Arg Asp Ile Lys Leu Ile Asp Val Glu Met Thr 465 470 475 480 Lys Glu Ala Ser Arg Glu Tyr Glu Asp Lys Val Trp Asp Lys Tyr Gly 485 490 495 Trp Leu Cys Lys Met His Thr Gly Val Val Arg Asp Lys Lys Lys Lys 500 505 510 Glu Ile Thr Pro His Cys Ala Leu Met Asp...

Claims

1. A lymphocytic choriomeningitis virus mutant, wherein the mutant comprises a nucleic acid encoding a glycoprotein, wherein compared with the wild-type glycoprotein sequence shown in SEQ ID NO: 10, the glycoprotein has only one or two mutations in the GP1 region, wherein the one mutation is Arg185→Trp, and the two mutations are Arg185→Trp and Ile181→Met.

2. The mutant of claim 1, wherein the mutant comprises a nucleic acid encoding a glycoprotein, wherein compared with the wild-type glycoprotein shown in SEQ ID NO: 10, two mutations occur in the GP1 region of the glycoprotein, and the two mutations are Arg185→Trp and Ile181→Met.

3. A mutant of lymphocytic choriomeningitis virus, wherein the mutant comprises a nucleic acid encoding a glycoprotein, wherein the glycoprotein is identical to the sequence shown in any one of SEQ ID NOs: 18, 26 and 50.

4. The mutant according to any one of the preceding claims, wherein the mutant comprises a nucleic acid encoding a glycoprotein, wherein the nucleic acid has a sequence identical to the sequence shown in any one of SEQ ID NOs: 17, 25, 33, 41, 49 and 57.

5. Use of the lymphocytic choriomeningitis virus mutant according to any one of claims 1 to 4 in the preparation of a medicament for treating and / or preventing tumors or cancers; wherein: The tumor or cancer is selected from fibrosarcoma, thyroid cancer, prostate cancer, lung cancer, melanoma, pancreatic cancer and oropharyngeal cancer.

6. A medicament or pharmaceutical composition comprising the lymphocytic choriomeningitis virus mutant according to any one of claims 1 to 4.

7. The medicament or pharmaceutical composition according to claim 6, characterized in that The medicament also comprises a checkpoint blocker and / or an apoptosis regulator.

8. The medicament or pharmaceutical composition according to claim 7, wherein The checkpoint is PD-1.

9. The medicament or pharmaceutical composition according to claim 7, wherein The apoptosis modulator is an apoptosis inhibitor.

10. The pharmaceutical agent or pharmaceutical composition according to claim 9, wherein The apoptosis inhibitor is a SMAC-mimetic.

11. A protein or peptide consisting of the amino acid sequence according to SEQ ID NO: 18, SEQ ID NO: 26 or SEQ ID NO:

50.

12. A nucleic acid, wherein the nucleic acid consists of a nucleic acid sequence according to SEQ ID NO: 17, SEQ ID NO: 25, SEQ ID NO: 33, SEQ ID NO: 41 or SEQ ID NO: 49 or a nucleic acid sequence complementary to said nucleic acid sequence.

13. A glycoprotein, compared with the wild-type lymphocytic choriomeningitis virus (LCMV) glycoprotein shown in SEQ ID NO: 10, the glycoprotein has only one or two mutations in the GP1 region, the one mutation is Arg185→Trp, and the two mutations are Arg185→Trp and Ile181→Met.

14. A nucleic acid comprising a nucleic acid sequence encoding a glycoprotein, wherein compared with the wild-type LCMV glycoprotein shown in SEQ ID NO: 10, the glycoprotein has only one or two mutations in the GP1 region, wherein the one mutation is Arg185→Trp, and the two mutations are Arg185→Trp and Ile181→Met.

15. A gene cluster or operon comprising the nucleic acid of claim 14.

16. An expression vector comprising the nucleic acid of claim 14 or the gene cluster or operon of claim 15.

17. An organism expressing or comprising the glycoprotein of claim 13 and / or comprising the nucleic acid of claim 14.

18. A virus expressing or comprising the glycoprotein of claim 13 and / or comprising the nucleic acid of claim 14.

19. A vector, said vector expressing or comprising the glycoprotein according to claim 13 and / or comprising the nucleic acid according to claim 14.

20. A plasmid comprising the nucleic acid of claim 14.

Images