The major goal of the work proposed is to understand the molecular basis of two fundamental processes involved in replication of enveloped animal viruses. These are 1), how viral glycoproteins are targeted to specific membranes where the virus assembles and 2), what interactions among viral components are important to efficient assembly of the virus at these specific membranes. The two viral systems that will be used in these studies are vesicular stomatitis virus (a rhabdovirus) and mouse hepatitis virus (a coronavirus). The approach to be taken includes the use of in vitro mutagenesis and eukaryctic gene expression systems to analyze the protein domains and modifications that are important in the transport of viral proteins to specific membranes and in the assembly of these proteins to specific membranes and in the assembly of these proteins into the virus particle. Both of the viruses to be studied are prototypes of groups that cause significant human disease. An understanding of the molecular basis of virus assembly may suggest ways to interfere specifically with virus replication, and may provide fundamental insight into normal cellular processes. In addition, an understanding of the interactions involved in efficient incorporation of glycoproteins into virus particles may suggest ways to engineer virus particles carrying novel proteins in their membranes. Such particles could be useful in targeting viral vectors to specific tissues.
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