The overall objective of the proposed research program is to define the events associated with the synthesis, processing and localization of the herpes simplex virus (HSV) specific glycoproteins within the virus-infected cell and the role which these glycoproteins may play in the induction of the immune response to HSV infections. The first major aspect concerns the organization and interaction of the glycoproteins associated with the envelope of the virion and the plasma membrane of the virus-infected cell. Approaches to be used include detergent solubilization of the glycoproteins from the membranes in the absence of denaturing reagents, the use of chemical cross-linkers, and the use of polar epithelial cells to identify the polarity of expression of HSV glycoproteins on the cell membrane. The second major aspect of the proposed study will focus on the cytoplasmic events associated with the intracellular processing of HSV glycoproteins. One aspect of these studies will include defining the kinetics of glycoprotein processing within HSV-1 infected cells. The other aspect will involve the use of inhibitors of the glucosidases involved with the removal of the terminal glucose residue from the newly synthesized oligosaccharide chain. The effect of this event on glycoprotein processing, localization and the envelopment process will be studied. The third major aspect of the proposed study concerns the association of HSV glycoproteins with the nuclear fraction of infected cells. The proposed experiments will a) involve the further characterization and significance of the posttranslational processing of the nonglycosylated precursors associated with the nuclear fraction, b) investigate by chemical cross-linking experiments the organization of the glycoproteins associated with the outer nuclear membrane of the infected cell, and c) study the possible role of certain cytoskeletal elements in the envelopment process of the virus particles. The fourth major aspect of the proposed study will involve studies on anti-idiotype antibodies produced to monoclonal antibodies specific for HSV glycoproteins. The potential role of these anti-idiotype antibodies in modulating the immune response to HSV in an animal model will be studied.
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