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

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