Human T cell leukemia virus type I (HTLV-I) is an exogenous retrovirus that is the etiologic agent of adult T cell leukemia in man. The overall goal of this study is to map antigenic sites on gp46 and gp21 envelope glycoproteins of HTLV-I that give rise to virus neutralizing antibodies and to evaluate in animals a synthetic vaccine containing these neutralizing sites. This study will also attempt to identify antigenic sites on HTLV-I proteins that are identified by T helper cells with peripheral blood leukocytes of HTLV-I+ patients and to incorporate these T cell sites into a synthetic vaccine. This study will also evaluate the prevalence of HTLV-I infection in individuals with AIDS, in hemophiliacs, and in individuals from sexually-transmitted disease (STD) clinics in North Carolina. Synthetic peptides containing hydrophilic amino acid sequences from HTLV-I gp46 and gp21 envelope proteins will be used to raise antisera in rabbits to viral envelope antigens. Anti-peptide antisera will be evaluated for reactivity to viral envelope and for the ability to inhibit both HTLV-I-induced synctium formation and the infectivity of HTLV-I (VSV) pseudotype particles. Antibodies in HTLV-I+ patient sera will be tested for reactivity to env-encoded synthetic peptides in radioimmunoassay (RIA) to map immunogenic sites in man. Techniques and reagents developed during the first three years of this grant will be used to purify gp46 from lysates of HTLV-I infected cells. Proteolytic fragments of gp46 characterized by amino acid sequence analysis will be used to immunize mice for the production of murine monoclonal antibodies to defined regions of gp46. Purified gp46 and polymers of gp46 will be tested for binding to surface of T cells and for the ability to induce resting peripheral blood T cells to undergo blast transformation. Purified gp46 will also be used with cross-linking agents to identify cell surface receptors for HTLV-I. Synthetic peptides containing sequences of HTLV-I proteins that are predicted to have amphipathic helical structures will be tested for the ability to induce blast tranformation of peripheral blood leukocytes from HTLV=I+ patients. RIA and immunoblot assays will be used to evaluate the prevalence of HTLV- I infection in AIDS patients, in hemophiliacs and in individuals from STD clinics in North Carolina.

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National Cancer Institute (NCI)
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Experimental Virology Study Section (EVR)
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Duke University
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