The role of vaccinia virus nucleoside triphosphate phosphohydrolase I (NPH-I) in determining the resistance of this virus to α-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-α 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.
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