Different effects of IFNγ and IFNα/β on “immediate early” gene expression of HSV-1

Abstract

The effects of interferon gamma (IFNγ) on early steps of herpes simplex virus (Type 1; HSV-1) replication in primary cultures of splenic mouse macrophages were analyzed and compared to IFNα/β. Pretreatment of macrophages with recombinant murine IFNγ led to a dose-dependent reduction in the yield of progeny virus. Inhibition of protein synthesis was observed for HSV-1α,β and γ-proteins. Expression of the “immediate early” (IE) gene IE3 (ICP4) was investigated in detail. Steady-state level of the RNA and transcriptional activity of the gene in IFNγ-treated cells were comparable to control-infected cells except for a delay in their kinetics. This is in contrast to IFNα/β, which leads to a stable decrease in IE3 transcripts. Since IFNγ causes a stable decrease in the IE3 gene product ICP4, our data suggest a translational inhibition of HSV-1 IE gene expression in IFNγ-treated macrophages. Thus, IFNγ and IFNα/β inhibit HSV-1 replication by different mechanisms which may lead to a synergistic enhancement of inhibition after combined treatment.