This application describes the ongoing research of four investigators who interact extensively, occupy adjoining laboratories, and work on various aspects of the molecular genetics of herpes simplex (HSV) and Epstein-Barr viruses. Project 1 centers on the domains and functions of HSV alpha genes, and on the function of genes nonessential for growth in cell culture. The work entails application of novel insertion/deletion techniques for deletion of genes from the viral genome and construction of cell lines expressing alpha genes for the study of their functions. Project 2 focuses on the HSV glycoproteins that govern the process of viral induced cell fusion. These studies have demonstrated that two glyco-proteins, B and D, play a major role in cell fusion and have led to the discovery and partial nucleotide sequence of a hitherto unidentified gene that also modulates the fusion process. Studies in progress are designed to identify the product of this gene. Project 3 focuses on host gene expression in HSV infected cells. A mutant defective in early host shut-off has been partially mapped and shown to act posttranslationally on both host and viral protein synthesis by destabilizing mRNA. Current studies focus on the product of the gene and on in vitro translational systems to characterize the destablilization of the RNA. Project 4 focuses on the use of HSV vectors to express EBV genes and on the glycoprotein genes of EBV. Current studies center on the characterization of the EBV gene products.
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