Pretreatment of HeLa cells with human interferon (IFN) resulted in the inhibition of herpes simplex virus (HSV) replication. We examined the stages in the replication of HSV type 1 and type 2 that were affected by IFN. The rate of synthesis of the HSV immediate-early (α) proteins was inhibited in IFN-pretreated HeLa cells. The subsequent inductions of HSV early (β) genes, determined by measuring the levels of cytoplasmic mRNA specific for the thymidine kinase, as well as the DNA polymerase enzyme activity, were also suppressed in the IFN-pretreated cells. These results indicate that IFN inhibits HSV replication primarily at a very early step, either prior to, or during the synthesis of α-proteins.


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