Viral Pathogenesis: Recent work on the structure and function of viral proteins has led to findings which suggest that peptides derived from viral structural and regulatory protein sequences can alter the regulation, both positively and negatively, of cell activation and physiologic response. Detailed characterization of the mechanism of these reactivities is in progress. Methodology and instrumentation have been designed and constructed to provide powerful, new analytical capabilities for measurement of virus receptor binding events, cellular adhesion, and other processes related to virus infection. Therapy: Applications to vaccine design and design of antivirals are being studied. Human immunodeficiency virus/Simian immunodeficiency virus/Human T-cell leukemia/lymphotropic virus protein sequences sensitive to neutralizing, non-neutralizing, and cross-reactive antibodies have been identified and their structural and functional determinants of activity are being determined. Aspects of cell-receptor binding of viral proteins, and related cellular factors e.g., chemokine receptors, cytokine receptors, and CD4, are being studied by combined approaches of peptide synthesis, high sensitivity binding studies, and molecular modeling. Identification of the receptor sequences engaged in binding virus and/or related cellular factors leads directly to inhibitors of virus infection or regulation as well as providing a means for studying mechanisms of resistance.
