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Inhibition of viral replication by nitric oxide and its reversal by ferrous sulfate and tricarboxylic acid cycle metabolites

IFN-gamma-induced nitric oxide (NO) in the murine macrophage-derived cell line RAW 264.7 was previously shown to inhibit replication of the poxviruses ectromelia and vaccinia (VV) and HSV-1. In the current study we demonstrate that murine macrophages activated as a consequence of VV infection expres...

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Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1995
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192048/
https://www.ncbi.nlm.nih.gov/pubmed/7539042
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description IFN-gamma-induced nitric oxide (NO) in the murine macrophage-derived cell line RAW 264.7 was previously shown to inhibit replication of the poxviruses ectromelia and vaccinia (VV) and HSV-1. In the current study we demonstrate that murine macrophages activated as a consequence of VV infection express inducible nitric oxide synthase. These activated macrophages were resistant to infection with VV and efficiently blocked the replication of VV and HSV-1 in infected bystander cells of epithelial and fibroblast origin. This inhibition was arginine dependent, correlated with nitrite production in cultures, and reversible by the NOS inhibitor N omega-monomethyl-L-arginine. NO- mediated inhibition of VV replication was studied by treatment of virus- infected human 293 cells with the NO donor S-nitroso-N-acetyl- penicillamine. Using a VV-specific DNA probe, antibodies specific for temporally expressed viral proteins, and transmission electron microscopy, we have shown that NO inhibited viral late gene protein synthesis, DNA replication, and virus particle formation, but not expression of the early proteins that were analyzed. Putative enzymatic targets of NO were identified by reversing the NO-mediated inhibition of VV replication in the 293 cells with exogenous ferrous sulfate and L- cysteine. Reversal of inhibition may derive from the capacity of these reagents to protect or regenerate nonheme iron or thiol groups, respectively, which are essential for the catalytic activities of enzymes susceptible to inactivation by NO.
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spelling pubmed-21920482008-04-16 Inhibition of viral replication by nitric oxide and its reversal by ferrous sulfate and tricarboxylic acid cycle metabolites J Exp Med Articles IFN-gamma-induced nitric oxide (NO) in the murine macrophage-derived cell line RAW 264.7 was previously shown to inhibit replication of the poxviruses ectromelia and vaccinia (VV) and HSV-1. In the current study we demonstrate that murine macrophages activated as a consequence of VV infection express inducible nitric oxide synthase. These activated macrophages were resistant to infection with VV and efficiently blocked the replication of VV and HSV-1 in infected bystander cells of epithelial and fibroblast origin. This inhibition was arginine dependent, correlated with nitrite production in cultures, and reversible by the NOS inhibitor N omega-monomethyl-L-arginine. NO- mediated inhibition of VV replication was studied by treatment of virus- infected human 293 cells with the NO donor S-nitroso-N-acetyl- penicillamine. Using a VV-specific DNA probe, antibodies specific for temporally expressed viral proteins, and transmission electron microscopy, we have shown that NO inhibited viral late gene protein synthesis, DNA replication, and virus particle formation, but not expression of the early proteins that were analyzed. Putative enzymatic targets of NO were identified by reversing the NO-mediated inhibition of VV replication in the 293 cells with exogenous ferrous sulfate and L- cysteine. Reversal of inhibition may derive from the capacity of these reagents to protect or regenerate nonheme iron or thiol groups, respectively, which are essential for the catalytic activities of enzymes susceptible to inactivation by NO. The Rockefeller University Press 1995-06-01 /pmc/articles/PMC2192048/ /pubmed/7539042 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Inhibition of viral replication by nitric oxide and its reversal by ferrous sulfate and tricarboxylic acid cycle metabolites
title Inhibition of viral replication by nitric oxide and its reversal by ferrous sulfate and tricarboxylic acid cycle metabolites
title_full Inhibition of viral replication by nitric oxide and its reversal by ferrous sulfate and tricarboxylic acid cycle metabolites
title_fullStr Inhibition of viral replication by nitric oxide and its reversal by ferrous sulfate and tricarboxylic acid cycle metabolites
title_full_unstemmed Inhibition of viral replication by nitric oxide and its reversal by ferrous sulfate and tricarboxylic acid cycle metabolites
title_short Inhibition of viral replication by nitric oxide and its reversal by ferrous sulfate and tricarboxylic acid cycle metabolites
title_sort inhibition of viral replication by nitric oxide and its reversal by ferrous sulfate and tricarboxylic acid cycle metabolites
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192048/
https://www.ncbi.nlm.nih.gov/pubmed/7539042