A mutation of the nucleoside triphosphate phosphohydrolase I (NPH-I) gene confers sensitivity of vaccinia virus to interferon.
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.
Díaz-Guerra
M
M
Department of Biochemistry, State University of New York, Brooklyn 11203.
Kahn
J S
JS
Esteban
M
M
D017766:Acid Anhydride Hydrolases / Q000235:genetics* / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004265:DNA Helicases; D004352:Drug Resistance, Microbial / Q000235:genetics*; D015870:Gene Expression; D005814:Genes, Viral; D000882:Haplorhini; D006801:Humans; D016898:Interferon-alpha / Q000633:toxicity*; D007739:L Cells; D008156:Luciferases / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D043583:Nucleoside-Triphosphatase; D015347:RNA Probes; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection; D014616:Vaccinia virus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*
D016898:Interferon-alpha; D015347:RNA Probes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D008156:Luciferases; D017766:Acid Anhydride Hydrolases; D000251:Adenosine Triphosphatases; D043583:Nucleoside-Triphosphatase; D004265:DNA Helicases