Abstract
The role of vaccinia virus nucleoside triphosphate phosphohydrolase I (NPH-I) in determining the resistance of this virus to alpha-interferon (IFN) was analyzed by using a well-defined temperature-sensitive mutant (ts36) in the NPH-I gene. Detailed analysis of viral proteins and mRNAs produced in cultured cells treated with or without IFN-alpha showed a strong inhibition by IFN of the synthesis of late virus polypeptides at the nonpermissive temperature, e.g., 83.8% inhibition for the luciferase reporter gene, which is associated with a decrease in steady-state mRNA levels. Sensitivity of ts36 to IFN was only the consequence of the point mutation in the NPH-1 gene, as shown by characterization of the rescued virus, R36. Our findings demonstrate that functional NPH-1 is required, at least in part, for resistance of vaccinia virus to IFN.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acid Anhydride Hydrolases / genetics*
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Acid Anhydride Hydrolases / metabolism
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Adenosine Triphosphatases / genetics*
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Adenosine Triphosphatases / metabolism
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Animals
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Cell Line
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DNA Helicases*
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Drug Resistance, Microbial / genetics*
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Gene Expression
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Genes, Viral*
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Haplorhini
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Humans
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Interferon-alpha / toxicity*
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L Cells
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Luciferases / biosynthesis
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Luciferases / metabolism
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Mice
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Nucleoside-Triphosphatase
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RNA Probes
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RNA, Messenger / metabolism
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / metabolism
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Transfection
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Vaccinia virus / drug effects*
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Vaccinia virus / enzymology
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Vaccinia virus / genetics*
Substances
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Interferon-alpha
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RNA Probes
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RNA, Messenger
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Recombinant Proteins
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Luciferases
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Acid Anhydride Hydrolases
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Adenosine Triphosphatases
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Nucleoside-Triphosphatase
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DNA Helicases