The focus of our research is the control of mRNA stability in mammalian cells and, specifically, in cells infected with herpes simplex virus (HSV). HSV encodes a polypeptide, the virion host shutoff (vhs) protein, that induces rapid turnover of both viral and cellular MRNAS in infected cells. In cells infected with HSV, mRNA levels are determined by both the rate of transcription and the rate of mRNA degradation. By regulating the rate of mRNA turnover, the vhs protein plays an important role in the overall scheme of gene regulation in infected cells. Our laboratory is investigating the mechanism of action of the vhs protein. This work involves site-specific mutagenesis of the cloned gene and testing the activities of the mutant proteins. The studies also involve utilization of an in vitro mRNA degradation system to study the process of vhs-induced mRNA turnover in biochemical detail. The work should add to the understanding of gene regulation during an HSV infection. In addition, the vhs function provides an attractive model system that should yield information concerning the control of mRNA stability in uninfected cells.