Expression of gamma interferon-dependent genes is blocked independently by virion host shutoff RNase and by US3 protein kinase.
Gamma interferon receptor alpha (IFN-gammaR alpha) 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-gammaR alpha is phosphorylated by the U(S)3 kinase. The modification is abolished in cells infected with DeltaU(S)3, DeltaU(L)13, or Delta(U(S)3/U(L)13) mutant virus. Transcripts of the IFN-gamma-dependent genes do not accumulate in cells transduced with the U(S)3 protein kinase and treated with IFN-gamma. In contrast, the accumulation of IFN-gamma-dependent gene transcripts is suppressed in cells infected with the wild-type virus, in cells infected with the DeltaU(S)3 mutant virus, and to a lesser extent in the DeltaU(L)41 virus-infected cells. The accumulation of IFN-gamma-dependent gene transcripts in DeltaU(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-gamma-dependent genes is blocked independently by the degradation of IFN-gamma-dependent gene transcripts--a function of the virion host shutoff RNase--and by posttranslational modification of the IFN-gammaR alpha protein.
Liang
Li
L
The Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, 910 East 58th Street, Chicago, IL 60637, USA.
Roizman
Bernard
B
D002460:Cell Line; D017353:Gene Deletion; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D017471:Receptors, Interferon / Q000378:metabolism; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism*; D018139:Simplexvirus / Q000235:genetics / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D017346:Protein Serine-Threonine Kinases; D017471:Receptors, Interferon; D012260:Ribonucleases; D014764:Viral Proteins; D000096743:Interferon gamma Receptor; C095207:US3 protein, Human herpesvirus 1