Inhibition of viral replication by interferon-gamma-induced nitric oxide synthase.
Interferons (IFNs) induce antiviral activity in many cell types. The ability of IFN-gamma to inhibit replication of ectromelia, vaccinia, and herpes simplex-1 viruses in mouse macrophages correlated with the cells' production of nitric oxide (NO). Viral replication was restored in IFN-gamma-treated macrophages exposed to inhibitors of NO synthase. Conversely, epithelial cells with no detectable NO synthesis restricted viral replication when transfected with a complementary DNA encoding inducible NO synthase or treated with organic compounds that generate NO. In mice, an inhibitor of NO synthase converted resolving ectromelia virus infection into fulminant mousepox. Thus, induction of NO synthase can be necessary and sufficient for a substantial antiviral effect of IFN-gamma.
Karupiah
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Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Xie
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Buller
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Nathan
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Duarte
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MacMicking
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D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D004481:Ectromelia virus / Q000187:drug effects / Q000502:physiology*; D004482:Ectromelia, Infectious / Q000382:microbiology; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D019001:Nitric Oxide Synthase; D018139:Simplexvirus / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D014616:Vaccinia virus / Q000187:drug effects / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases