HIV Antigens for Disease Intervention.
Final rept. 28 Sep 90-27 Sep 93,
HARVARD SCHOOL OF PUBLIC HEALTH BOSTON MA DEPT OF ENVIRONMENTAL HEALTH SCIENC ES
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The HIV-1 Env gene encodes a 160 KD glycoprotein precursor, which is subsequently cleaved into two smaller species the extracellular protein gp120 and the transmembrane protein gp41. HIV-1 vaccine development efforts conducted in this contract include developing strategies of modifying the antigenicity of HIV envelope protein. The approaches adopted involve analysis of the possible function for N-linked glycosylation sites of gp 120 and gp41. The data obtained support our hypothesis that N-linked sugars may be present to help virus evade immune system. We also analyzed the role of hypervariable domains and other gpl2O residues in the formation of broadly neutralizing antigenic epitope. The method of selectively removing virus infectivity-enhancing antigenic epitope from gp4l was also identified. Another line of research conducted involves the study of structure-function relationship of gp41. The role of N-linked sugars. a leucine zipper structure motif and the long cytoplasmic domain of gp4l in virus assembly, virus infectivity and in the formation of envelope oligomers were identified. In addition, we conducted studies to compare the cytopathicity of macrophage-tropic, non-syncytium-inducing HIV-1 and T cell-line tropic, syncytium-inducing HIV-1 and conclude that both classes of HIV-1 can have direct roles in the depletion of T4 cells. HIV, Envelope, GP120, Vaccine development, AIDS, Vaccines, Biotechnology, RAD I
- Biomedical Instrumentation and Bioengineering
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research