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Title[redir]:
Analysis of the MCMV resistome by ENU mutagenesis | Mammalian Genome
Description:
The mouse cytomegalovirus (MCMV) resistome is the set of host genes with nonredundant functions in resistance to MCMV infection. By screening 3500 G3 germline mutant mice (∼1750 gamete equivalents), we have identified eight transmissible mutations that create MCMV susceptibility in C57BL/6 mice. Among these, a mutation called Domino was noted to cause macrophage susceptibility to vesicular stomatitis virus (VSV) in vitro. This accessory phenotype was not corrected by type I interferon (IFN), which suggested a defect of the type I IFN pathway. Domino corresponds to a point mutation that alters the DNA binding domain of STAT1, leading to a defect of STAT1 activation. Identification of the Domino mutation demonstrates that an in vivo MCMV susceptibility screen is feasible and illustrates how it can provide insight into the resistome. Moreover, some mutations are far more deleterious than Domino in MCMV-infected mice, consistent with the interpretation that certain protein(s) unrelated to IFN production or signaling are more important than IFNs with regard to their net antiviral effects.
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Keywords {🔍}
article, cas, pubmed, google, scholar, mouse, cytomegalovirus, mcmv, infection, stat, mice, cell, cells, natural, killer, function, georgel, interferon, access, murine, usa, genes, mutation, gene, viral, privacy, cookies, content, susceptibility, domino, virus, ifn, immunol, proc, natl, acad, sci, innate, immunity, exp, med, author, analysis, information, publish, research, search, genome, resistome, mutagenesis,
Topics {✒️}
vesicular stomatitis virus arginine/lysine-rich structural element month download article/chapter kasper hoebe & bruce beutler natural killer cells analyzing gene function karap/dap12 adaptor molecule early cytokine responses full article pdf nonredundant functions accessory phenotype cmv1-independent antiviral role philippe georgel create mcmv susceptibility c-type lectin superfamily ifn-alpha/beta genes m25 gene products interferon-induced nuclear import dna binding domain distinct interferon-alpha genes nk cell responses related subjects jak-stat signaling pathway virus-encoded ligand scripps research institute mouse cell monolayers privacy choices/manage cookies murine cytomegalovirus infection mouse peritoneal macrophages darnell je jr author correspondence mouse cytomegalovirus infection lee sh enu mutagenesis published check access instant access ifn-alpha/beta dominant egfr mutation mouse genome informatics dual function stat transcription factors mouse spot test innate immune responses interferon regulatory factor-7 stat1 transcription factor mcmv virus murine cytomegalovirus-infected interferon-alpha/beta mutation called domino domino mutation demonstrates
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headline:Analysis of the MCMV resistome by ENU mutagenesis
description:The mouse cytomegalovirus (MCMV) resistome is the set of host genes with nonredundant functions in resistance to MCMV infection. By screening 3500 G3 germline mutant mice (∼1750 gamete equivalents), we have identified eight transmissible mutations that create MCMV susceptibility in C57BL/6 mice. Among these, a mutation called Domino was noted to cause macrophage susceptibility to vesicular stomatitis virus (VSV) in vitro. This accessory phenotype was not corrected by type I interferon (IFN), which suggested a defect of the type I IFN pathway. Domino corresponds to a point mutation that alters the DNA binding domain of STAT1, leading to a defect of STAT1 activation. Identification of the Domino mutation demonstrates that an in vivo MCMV susceptibility screen is feasible and illustrates how it can provide insight into the resistome. Moreover, some mutations are far more deleterious than Domino in MCMV-infected mice, consistent with the interpretation that certain protein(s) unrelated to IFN production or signaling are more important than IFNs with regard to their net antiviral effects.
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Vesicular Stomatitis Virus
Natural Killer Cell Function
Susceptibility Phenotype
MCMV Infection
Nonredundant Function
Cell Biology
Animal Genetics and Genomics
Human Genetics
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headline:Analysis of the MCMV resistome by ENU mutagenesis
description:The mouse cytomegalovirus (MCMV) resistome is the set of host genes with nonredundant functions in resistance to MCMV infection. By screening 3500 G3 germline mutant mice (∼1750 gamete equivalents), we have identified eight transmissible mutations that create MCMV susceptibility in C57BL/6 mice. Among these, a mutation called Domino was noted to cause macrophage susceptibility to vesicular stomatitis virus (VSV) in vitro. This accessory phenotype was not corrected by type I interferon (IFN), which suggested a defect of the type I IFN pathway. Domino corresponds to a point mutation that alters the DNA binding domain of STAT1, leading to a defect of STAT1 activation. Identification of the Domino mutation demonstrates that an in vivo MCMV susceptibility screen is feasible and illustrates how it can provide insight into the resistome. Moreover, some mutations are far more deleterious than Domino in MCMV-infected mice, consistent with the interpretation that certain protein(s) unrelated to IFN production or signaling are more important than IFNs with regard to their net antiviral effects.
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Natural Killer Cell Function
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Human Genetics
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