Expression of Gamma Interferon-Dependent Genes Is Blocked Independently by Virion Host Shutoff RNase and by U S 3 Protein Kinase

Abstract

ABSTRACT Gamma interferon receptor α (IFN-γRα) is stable but posttranslationally modified in herpes simplex virus 1(F) [HSV-1(F)]-infected cells. Studies with antibody directed to the phosphorylation site indicate that IFN-γRα is phosphorylated by the U S 3 kinase. The modification is abolished in cells infected with ΔU S 3, ΔU L 13, or Δ(U S 3/U L 13) mutant virus. Transcripts of the IFN-γ-dependent genes do not accumulate in cells transduced with the U S 3 protein kinase and treated with IFN-γ. In contrast, the accumulation of IFN-γ-dependent gene transcripts is suppressed in cells infected with the wild-type virus, in cells infected with the ΔU S 3 mutant virus, and to a lesser extent in the ΔU L 41 virus-infected cells. The accumulation of IFN-γ-dependent gene transcripts in ΔU L 41-infected cells could be due at least in part to a significant delay and reduction in the accumulation of the U S 3 protein. The results suggest that the expression of IFN-γ-dependent genes is blocked independently by the degradation of IFN-γ-dependent gene transcripts—a function of the virion host shutoff RNase—and by posttranslational modification of the IFN-γRα protein.