36 results about "ISG15" patented technology

The invention relates to a detection system for detecting a human immune state and belongs to the technical field of gene detection. The detection system provided by the invention is used for detecting 20 genes, including IFI27, ISG15, IFI44L, RSAD2, HERC5, IFITM3, IFI44, IFIT3, EPSTI1, IFIT1, HP, ANXA3, ARG1, FCGR1B, S100A12, MMP9, IL18R1, TLR3, GYG1 AND FCGR1A in peripheral blood; the assessment for the human immune state can be realized in the manner of increasing or reducing the expression level of each gene; and the genes are utilized to guide accurate medical treatment, including disease accurate parting, prognosis, treatment tracking and therapeutic evaluation. The detection system has excellent clinic application values and wide application prospects.

The invention belongs to the technical field of the livestock genetic engineering, and particularly relates to the molecular mark used as auxiliary choice of pig marks and relating to immunity and reproductive trait and application thereof. The molecular mark is obtained from ISG15 gene clone, and the cDNA sequence thereof is described in a sequence list SEQ ID NO: 1. A base mutation of A390-G390 exists in a 390bp place of the sequence list SEQ ID NO: 1, thereby resulting in the HindIII-RFLP polymorphism. The invention also discloses the primers used by the HindIII-RFLP polymorphism and a polymorphism detection method, and provides a new molecular mark for the auxiliary choice of pig marks.

The invention relates to an in vitro method of predicting the therapeutic effect of interferon treatment on a patient with hepatitis C, which belongs to the in vitro diagnostic reagent category of the biological medicine and is a substantive improvement based on a patent being applied for at present. The interferon treatment is effective only for 50 percent of patients with hepatitis C. The clinical operation is short of a method of predicting the therapeutic effect before the treatment of hepatitis C. According to the positioning and analysis of the expression of the ISG15 or MxA protein in the liver tissue through the immunohistochemical technique before the treatment of patients with hepatitis C, the distributions of ISG15 or MxA are different in the liver tissues of the patients for whom the interferon treatment is effective and the patients for whom the interferon treatment is not effective: the expression of the genes in the liver cells indicates that the interferon treatment is not effective for the patients; and the expression of the genes in the macrophage cells indicates that the interferon treatment is effective for the patients. The method is used to predict the therapeutic effects of the interferon treatment on 31 patients with hepatitis C, and the rate of accuracy reaches 100 percent. The invention can predict whether the patient with hepatitis C is sensitive to the interferon treatment before the interferon treatment, thereby optimizing the patient management.

Viruses having an impaired ability to deISGylate ISG15 conjugates, in particular, viral mutants comprising a mutation in the viral genome that reduces or eliminates the ability of the viral OTU domain-containing protein encoded by the viral genome to deISGylate ISG15 conjugates and / or deubiquitinate ubiquitinated proteins and / or deNeddylate Neddylated proteins are disclosed. Such viral mutants may be used in the formulation of immunogenic compositions for inducing an immune response and preventing, managing and / or treating a viral infection. Also disclosed are methods for identifying anti-viral compounds, in particular, methods of identifying compounds that reduce or inhibit the deISGylation activity and / or deubiquitination and / or deNeddylation activity of a viral OTU domain-containing protein. The compounds identified using such methods may be used as antiviral agents for the prevention, treatment and / or management of viral infections.

The invention belongs to the technical field of biology, and particularly relates to application of African swine fever virus E120R protein as an immunosuppressant and construction of an immunosuppression site knockout strain. The invention firstly discovers that the African swine fever virus E120R protein can inhibit activation of IFN-beta induced by cGAS / STING and poly (dA: dT), inhibit mRNA expression of IFN-beta induced by cGAS / STING and poly (dA: dT) and downstream factors ISG56 and ISG15 thereof, inhibit phosphorylation of IRF3 induced by cGAS / STING and poly (dA: dT), has a relatively strong immunosuppression effect, and can be used as an immunosuppressant; and secondly, the invention discovers an immunosuppression site of the African swine fever virus E120R protein, and constructs an African swine fever recombinant virus with the knockout of the immunosuppression site of the E120R protein through a genetic engineering means, the natural immunity of the African swine fever recombinant virus is significantly enhanced, and the African swine fever recombinant virus can be used as a recombinant vaccine strain, can promote early immune response, induce the production of high-levelantibodies, improve the biological safety and immune protection efficacy, and has good application prospects.

The present invention provides methods for detecting and treating cancer. In some embodiments, levels of ISG15 are determined, and topoisomerase I and II inhibitors as well as other DNA-damaging agents plus agents that increase the expression of ISG15 are selected and administered.

The invention belongs to the technical field of biology, and particularly relates to construction of an E184L gene deletion attenuated African swine fever virus strain and an application of the E184Lgene deletion attenuated African swine fever virus strain as a vaccine. The inventor firstly finds that an African swine fever virus E184L protein can inhibit the activation of poly (dA: dT)-induced IFN-beta, NF-kappa B and ISRE promoters, inhibits generation of poly (dA: dT)-induced IFN-beta and downstream factors ISG15, ISG54, IL-6, MCP1, TNF-alpha and other cytokines, has strong immunosuppressive effect, and can be used as an immunosuppressive; secondly, the immunosuppressive function of an E184L gene encoding protein is deleted from the African swine fever parent strain ASFV CN / GS / 2018 through a genetic engineering means, so that the immunosuppressive activity of the parent strain is reduced, and an attenuated African swine fever candidate vaccine strain with high safety is obtained; and after the attenuated African swine fever candidate vaccine strain is used for immunizing pigs, the immunosuppressive activity and pathogenicity of the pigs are reduced, remarkable neutralizing antibodies can be induced to be generated after immunization, and the attenuated African swine fever candidate vaccine strain can be used as a safe and effective candidate vaccine strain for preventing and controlling African swine fever epidemic situations and has great social value.

Disclosed herein is a vaccine comprising an antigen and ISG15. Also disclosed herein is a method for increasing an immune response in a subject in need thereof. Further disclosed herein is a method for treating a subject in need thereof. The methods may comprise administering the vaccine to the subject.

The present invention relates to compositions and methods for the modulation of both ubiquitin and ubiquitin-like protein mediated modification and degradation of target proteins that includes the steps of contacting the compound with an Ubiquitin-like protein E2 enzyme and an E1 enzyme containing an ISG15 protein and an E1 containing ubiquitin and detecting the effect of the compound on the interaction between the Ubiquitin-like protein E2 enzyme and these two E1 enzymes, and the steps of contacting the compound with an Ubiquitin-like E2 enzyme containing an ISG15 protein or the same E2 enzyme containing ubiquitin and the E3 enymes that function with this E2 enzyme and detecting the effect of the compound on the interaction between these E2 and E3 enzymes.

The genetically modified hemorrhagic fever virus of this invention possesses a viral ovarian tumor protease with decreased ability to remove ubiquitin (Ub) and ISG15 tags that the human organism uses to label proteins for removal. Unlike complete knockout strains, the modified virus retains enough activity for replication in a human cell line. This creates an immunogenic and non-pathogenic virus that can be used as an effective live vaccine agent.

The genetically modified nairoviruses of this invention possesses a viral ovarian tumor protease with decreased ability to remove ubiquitin (Ub) and ISG15 tags that the human organism uses to label proteins for removal. Exemplary are Crimean-Congo hemorrhagic fever virus and Erve virus. Unlike complete knockout strains, the modified virus retains enough activity for replication in a human cell line. This creates an immunogenic and non-pathogenic virus that can be used as an effective live vaccine agent for prophylaxis and treatment.

The present invention provides a skin test method for predicting the formation of spots in the skin. This method judges skin to be susceptible to the formation of spots in the case expression in the epidermis of MCP-2 gene, a polynucleotide capable of hybridizing under highly stringent conditions to mouse AK012157 gene, human FLJ21763 gene or rat S74257 gene, or Mcp9, Mcp10, Isg15, Usp18, Oas12, Gbp2, Gtpi, Ifi47, Igtp, Tgtp, Sprr2A, Krt2-6b, Cdk5rap2, Mef2C, Gsta4, Osf2, Tnc, Igfbp6, Ppicap or Mm. 74656 gene, is increased as compared with normal expression in the epidermis.

The genetically modified hemorrhagic fever virus of this invention possesses a viral ovarian tumor protease with decreased ability to remove ubiquitin (Ub) and ISG15 tags that the human organism uses to label proteins for removal. Unlike complete knockout strains, the modified virus retains enough activity for replication in a human cell line. This creates an immunogenic and non-pathogenic virus that can be used as an effective live vaccine agent.

The invention discloses an application of ZNF383 protein in preparing a product for inhibiting the activity of p53 protein. An experiment proves that the ZNF383 protein can inhibit the activity of the p53 protein, can lower an expression quantity of apoptosis-associated target genes (such as puma genes or p53 AIPI genes), can lower the expression quantity of immune-associated target genes (such as IRF5 genes, ISG15 genes or IFN-beta genes), can lower an expression level of the puma protein, and can inhibit the binding of a p53 protein-associated signal pass and the p53 protein. Therefore, the ZNF383 protein has important application value in preparing the product for inhibiting the activity of the p53 protein.

The invention provides a stable polypeptide protein covalent inhibitor of papain-like protease PLpro targeting 2019 novel coronavirus. The invention also provides application of the stable polypeptide protein covalent inhibitor in preparing a drug for inhibiting the enzyme activity of the papain-like protease PLpro. The invention adopts a method of reacting methionine-cysteine on polypeptide with a dialkylating reagent to form a single sulfonium salt to stabilize sulfonium salt cyclopeptide targeting PLpro. The invention adopts a strategy of coupling the sulfonium salt stable polypeptide with small molecules to invent the novel stable polypeptide protein covalent inhibitor of the papain-like protease PLpro. The polypeptide protein covalent inhibitor provided by the invention can effectively inhibit the activity of the papain-like protease PLpro, thereby blocking the immune escape reaction generated by cutting ISG15 by the papain-like protease PLpro.

The invention relates to a method for inhibiting cellular expression of Ifn[beta], Isg15, Gbp-1, Oas2, Irf7, Isg20 and Ifn4. The invention relates to the field of biological medicine, and in particular relates to a method for inhibiting the cellular expression of antiviral gene cells and the method is screened by measuring the expression quantities of Ifn[beta], Isg15, Gbp-1, Oas2, Irf7, Isg20 and Ifn4 and by constructing a vesicular stomatitis virus susceptible cell model caused by overexpression of RXRs (retinoid X receptors). The invention provides a constructing method of the vesicular stomatitis virus susceptible cell model caused by the overexpression of the RXRs, and applications of the RXRs in screening the method for inhibiting the cellular expression of the Ifn[beta], Isg15, Gbp-1, Oas2, Irf7, Isg20 and Ifn4, and finds that a COX sensing pathway inhibits antiviral genes in a host immune defense system through an RXR-dependent manner, and therefore, the practical application value of the RXRs in screening the method for inhibiting the cellular expression of the Ifn[beta], Isg15, Gbp-1, Oas2, Irf7, Isg20 and Ifn4 is further confirmed.

The invention especially relates to application of RXR in screening of agonists of Ifnbeta, Isg15, Gbp-1, Oas2, Irf7, Isg20 and Ifn4, which belongs to the field of biological medicine. The invention provides application of RXR in screening of agonists of Ifnbeta, Isg15, Gbp-1, Oas2, Irf7, Isg20 and Ifn4 and a construction method for a susceptible cell model representing down-regulated expression of antiviral genes like Ifnbeta, Isg15, Gbp-1, Oas2, Irf7, Isg20 and Ifn4 caused by overexpression of RXR. It is found that a COX susception pathway exerts inhibitory effect on antiviral genes in a host immune defense system in an RXR-dependent manner. Application of RXR in screening of the agonists of Ifnbeta, Isg15, Gbp-1, Oas2, Irf7, Isg20 and Ifn4 is further expounded.

The invention belongs to the field of biotechnology, and in particular relates to the construction of E184L gene deletion attenuated African swine fever virus strain and its application as a vaccine. The present invention first discovered that the African swine fever virus E184L protein can inhibit poly(dA:dT)-induced activation of IFN-β, NF-κB and ISRE promoters, inhibit poly(dA:dT)-induced IFN-β and its downstream The production of cytokines such as factors ISG15, ISG54, IL-6, MCP1 and TNF-α has a strong immunosuppressive effect and can be used as an immunosuppressant application; secondly, the present invention has the effect of genetic engineering on the African swine fever parent strain ASFV In CN / GS / 2018, the immunosuppressive function of the protein encoded by the E184L gene was deleted, which reduced the immunosuppressive activity of the parental strain, and obtained a highly safe attenuated African swine fever candidate vaccine strain; the attenuated African swine fever After the candidate vaccine strain immunizes pigs, it reduces the immunosuppressive activity and pathogenicity of pigs, and can induce significant neutralizing antibody production after immunization. It can be used as a safe and effective candidate vaccine strain for the prevention and control of African swine fever. great social value.

The present invention relates to kits, arrays, compositions and methods for predicting, assessing and evaluating responsiveness and success of interferon treatment as well as for monitoring disease progression and pathophysiology in a subject treated with interferon, using OAS2, HERC5, UPS18, UBE2L6 and optionally of ISG15 genes as biomarkers.

The invention belongs to the technical field of gene engineering, and particularly discloses a domestic pig ISG15 recombination protein and an encoding gene, a recombination plasmid, a recombination strain and application thereof. An amino acid sequence of the domestic pig ISG15 reconstruction protein is shown in SEQ ID No.2. A gene of the domestic pig ISG15 recombination protein, and the recombination plasmid and the recombination strain containing the gene are encoded. One of the domestic pig ISG15 recombination protein, the gene, the recombination plasmid and the recombination strain is applied to prepare a medicine for treating PR (pseudorabies). The domestic pig ISG15 recombination protein has the advantages that the antigen amount of the PRV (pseudorabies virus) is effectively reduced, the acute infection of the PRV is effectively controlled, and a new path is provided for controlling the virus infection.

Disclosed herein is a vaccine comprising an antigen and ISG15. Also disclosed herein is a method for increasing an immune response in a subject in need thereof. Further disclosed herein is a method for treating a subject in need thereof. The methods may comprise administering the vaccine to the subject.

The invention discloses application of African swine fever virus D205R and D345L genes, and particularly relates to application of the African swine fever virus D205R and D345L genes in preparation of an African swine fever virus vaccine. The African swine fever virus D205R and D345L genes can significantly inhibit virus infection induced interferon expression, and inhibit interferon stimulation gene ISGs expression. Through dual-luciferase reporter gene system detection, the invention finds that through comparison, sendai-virus-induced interferon promoter activity and interferon stimulation response element (ISRE) activity can be inhibited through expression of the D205R and D345L genes. The fluorescent quantitative PCR test finds that the expression of the D205R and D345L genes can significantly inhibit the mRNA expression level of I-type interferon IFNbeta induced by Sendai virus infection, and inhibit the expression level of interferon stimulating genes ISG15 and OASL playing an antiviral function; and in conclusion, two kinds of African swine fever virus proteins with the function of inhibiting host cell antiviral innate immune response are identified, and a new choice is provided for preparing an African swine fever virus gene deletion vaccine.

The invention belongs to the technical field of the livestock genetic engineering, and particularly relates to the molecular mark used as auxiliary choice of pig marks and relating to immunity and reproductive trait and application thereof. The molecular mark is obtained from ISG15 gene clone, and the cDNA sequence thereof is described in a sequence list SEQ ID NO: 1. A base mutation of A390-G390 exists in a 390bp place of the sequence list SEQ ID NO: 1, thereby resulting in the HindIII-RFLP polymorphism. The invention also discloses the primers used by the HindIII-RFLP polymorphism and a polymorphism detection method, and provides a new molecular mark for the auxiliary choice of pig marks.

Viruses having an impaired ability to deISGylate ISG15 conjugates, in particular, viral mutants comprising a mutation in the viral genome that reduces or eliminates the ability of the viral OTU domain-containing protein encoded by the viral genome to deISGylate ISG15 conjugates and / or deubiquitinate ubiquitinated proteins and / or deNeddylate Neddylated proteins are disclosed. Such viral mutants may be used in the formulation of immunogenic compositions for inducing an immune response and preventing, managing and / or treating a viral infection. Also disclosed are methods for identifying anti-viral compounds, in particular, methods of identifying compounds that reduce or inhibit the deISGylation activity and / or deubiquitination and / or deNeddylation activity of a viral OTU domain-containing protein. The compounds identified using such methods may be used as antiviral agents for the prevention, treatment and / or management of viral infections.

Methods are provided for assessing risk of developing esophageal adenocarcinoma in a subject using one or more of the following marker genes / proteins: ISG15, LTF, CNDP2, DAD1, SET, UBE2N, S100P, and GPI. Methods are also provided for determining expression of one or more esophageal adenocarcinoma risk factors in a subject. Methods are also provided for treating esophageal adenocarcinoma in a subject, for preventing esophageal adenocarcinoma in a subject, for inhibiting or decreasing proliferation of esophageal adenocarcinoma cells, for inhibiting or decreasing migration of esophageal adenocarcinoma cells, or for increasing susceptibility to cytotoxicity or inducing cell death of esophageal adenocarcinoma cells.

The invention provides a method for screening Ifn[beta], Isg15, Gbp-1, Oas2, Irf7, Isg20 and Ifn4 agonists and antagonists. The invention relates to the field of biological medicine, and in particular relates to a method for screening antiviral gene agonists and antagonists by measuring the expression quantities of Ifn[beta], Isg15, Gbp-1, Oas2, Irf7, Isg20 and Ifn4and by constructing a vesicular stomatitis virus susceptible cell model caused by overexpression of RXRs (retinoid X receptors). The invention provides a constructing method of the vesicular stomatitis virus susceptible cell model caused by the overexpression of the RXRs, and applications of the RXRs in screening the Ifn[beta], Isg15, Gbp-1, Oas2, Irf7, Isg20 and Ifn4 agonists, and finds that a COX sensing pathway inhibits antiviral genes in a host immune defense system through an RXR-dependent manner, and therefore, the practical application value of the RXRs in screening the Ifn[beta], Isg15, Gbp-1, Oas2, Irf7, Isg20 and Ifn4 agonists is further confirmed.

The invention relates to a detection system for detecting a human immune state and belongs to the technical field of gene detection. The detection system provided by the invention is used for detecting 20 genes, including IFI27, ISG15, IFI44L, RSAD2, HERC5, IFITM3, IFI44, IFIT3, EPSTI1, IFIT1, HP, ANXA3, ARG1, FCGR1B, S100A12, MMP9, IL18R1, TLR3, GYG1 AND FCGR1A in peripheral blood; the assessment for the human immune state can be realized in the manner of increasing or reducing the expression level of each gene; and the genes are utilized to guide accurate medical treatment, including disease accurate parting, prognosis, treatment tracking and therapeutic evaluation. The detection system has excellent clinic application values and wide application prospects.