Viral Pathogenesis: Recent work on the structure and function of viral proteins has led to the finding that peptide subcomponents within viral structural and regulatory protein sequences can alter the regulation, both positively and negatively, of cell activation and physiologic response, which can be monitored by intracellular Ca++ flux. Detailed characterization of the mechanism of these reactivities is in progress. Human immunodeficiency virus/simian immunodeficiency virus/human T-cell leukemia/lymphotropic virus protein binding sites of neutralizing, non-neutralizing, and cross-reactive antibodies have been identified and their structural and functional properties are being determined. Methodology and instrumentation have been designed and installed to provide powerful, new analytical capabilities for measurement of cellular adhesion, intracellular signaling and other processes related to virus infection and alteration of normal growth, tumor cell growth, and metastatic processes. Therapy: Applications to vaccine design and molecular epidemiology are being studied. Aspects of cell-receptor binding and signaling responses to viral proteins, and related physiologic response modifiers; e.g., basic fibroblast growth factor and extracellular matrix proteins, are being studied by combined approaches of peptide synthesis, physiological function, and molecular modeling. By identification of the receptor-binding sequence and structure of biologically active viral proteins and related biologic response modifiers, new drugs can be developed and mechanisms of resistance studied. Antisense oligonucleotides with tissue-specific affinity, antiviral activity or activities against other genes with oncogenic potential are being developed.
