The long term goals of this research are to understand the structure, intracellular transport and metabolism and function of the major DNA binding protein of herpes simplex virus (HSV). In this proposal we outline our approaches to determine whether there are distinct functional domains of the protein involved in the transport of the protein to the cell nucleus as opposed to its binding to viral DNA. We will use genetic and biochemical analysis of the viral gene product in these experiments. We also propose to further map and define the gene encoding this protein through the mapping and analysis of its mRNA transcript. We also propose to use this system as a model for the study of the nuclear transport of proteins. We will define the cellular interactions of wild type and mutant viral proteins with the host cell to understand the route and mechanism of accumulation of specific proteins in the cell nucleus. This viral gene product may also be of clinical importance in that an antigenically related protein has been detected in HSV transformed cells, cervical carcinoma tissue and vulvar carcinoma tissue. Thus this viral gene product may play a role in the transformation or tumorigenic process. Whether or not this protein is involved in the initiation of these neoplastic converstions, the protein could affect the metabolism of the transformed or tumor cells. We propose experiments to study the properties of the viral gene product to better predict its effect on the metabolism of a transformed cell.
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