Rous sarcoma virus encodes two surface proteins (gp85 or SU and gp37 or TM) that play a critical role in the replication cycle of the virus. The larger of the two molecules defines the host range of the virus by binding to a host cell-encoded receptor, while the smaller protein anchors gp85 in the viral membrane and functions in the process of virus-cell membrane fusion. The envelop glycoprotein (env) gene product (Pr95) is synthesized as a core-glycosylated polyprotein precursor that rapidly associates with other env precursors into a discreet homotrimeric complex with the endoplasmic reticulum-- a process that appears to be important for both intracellular transport and stabilization of a biologically active conformation. The major goals of this proposal are to understand the structural features of the Rous sarcoma virus envelope glycoprotein that direct the processes of precursor oligomerization, intracellular transport and targeting, and assembly of the mature glycoprotein complexes into budding virus. Specifically, he will characterize the domain within gp37 that directs the assembly of env trimers in the endoplasmic reticulum. He will determine the role of sequences in the cytoplasmic domain of gp37 in directing intracellular transport, endocytosis and lysosomal degradation of env. Lastly, he will determine the factors that modulate glycoprotein incorporation into virions and route of entry into cells.
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