investigator=s abstract): The goal of this proposal is to elucidate the role of Gag proteins in virion assembly, virus-induced cytopathicity, virus host -range and early steps of virus transmission. Preliminary studies indicate the Gag polyprotein, and in particular its matrix domain, has a central role in controlling HIV-1 induced cytopathicity. Furthermore, data show that matrix, and its interaction partner, the cytoplasmic domain of the viral envelope glycoprotein, can have major effects on the target cell tropism of HIV-1. To elucidate the basis for this novel role of Gag, which may have important implications for HIV-1 pathogenicity, the investigator proposes to investigate whether there is a connection between the role of Gag in viral cytopathicity and viral host range. In addition, the investigator has developed a method for efficient purification of intact HIV-1 virion cores and proposes to examine their protein composition and structure.
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