Herpesvirus infections of humans are among the most common of all human infections and can result in life-threatening diseases, although infrequently. This family of viruses is of great scientific interest because of their prevalence and unique propensity to establish latency and recur, even in the presence of humoral antibodies and cell mediated immunity. We have demonstrated that cloned human interferons (IFNs) block herpes simplex virus type 1 (HSV-1) replication at the stage of virus assembly and budding, probably through specific inhibition of viral glycoproteins. In addition, we have also suggested that these IFNs block HSV-1-mediated cell fusion via a similar mechanism. The goals of this project are to obtain a detailed understanding of how recombinant human IFNs affect the expression of specific HSV-glycoproteins such that these two important biological functions, replication and cell fusion, are prevented. First the viral glycoprotein synthesis and the expression and structure of viral glycoprotein mRNAs in IFN-treated cells will be analysed in order to pinpoint the exact nature of the glycoprotein inhibition in IFN-treated cells. Second, immunological and biochemical experiments will be performed to demonstrate the location of specific HSV-glycoprotein(s) in IFN-treated in comparison to untreated cells. Finally, the roles of glycoproteins in viral assembly and in induction of cell fusion will be studied through mammalian cell lines expressing cloned glycoprotein genes and by the analysis of deletion mutants in these glycoprotein genes.
