Human immunodeficiency virus type I (HIV), the etiological agent of the acquired immune deficiency syndrome (AIDS), has an envelope glycoprotein that is unusually highly glycosylated. Preliminary evidence indicates that the carbohydrate of this envelope glycoprotein has a preponderance of structures not normally found in abundance on cell surface components. These and other considerations described in the proposal suggest that carbohydrate components of HIV function critically in the pathogenesis of the virus. The goal of this proposal is to determine the structure of the carbohydrate components of the envelope glycoprotein of HIV and of CD4, the glycoprotein that serves as the receptor for HIV, and to obtain information about the role of the carbohydrate components in the pathogenesis of the virus. The objectives of this proposal related directly to the development of vaccines and anti-viral drugs, as it is likely that the extensive glycosylation of the exterior glycoprotein of the virus is one reason it is not destroyed by the natural immune response of the host. The proposal objectives are also relevant to understanding the importance of variation in the amino acid sequence of the envelope glycoprotein and any resulting variation in the structures and distribution of carbohydrate components, to the biology of HIV replication and pathogenesis. To address the proposed research, we have assembled a team of scientists with complementary skills to bring the combined power of contemporary molecular genetics, industrial scale biotechnology, and analytical chemistry to the project. The team includes the Dana-Farber Cancer Institute group, expert in molecular genetics with an established record of achievement in studies of the structure and function of the HIV envelope glycoprotein; a biotechnology company, Cambridge BioScience, with expertise in large scale production of proteins produced by recombinant DNA methods and particular skill in preparation of large amounts of HIV envelope glycoprotein polypeptides; and a group at the University of Georgia Complex Carbohydrate Research Center, expert in the structural analysis of the complex carbohydrate components of glycoproteins.
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