Individuals infected with HIV-1 display a wide range in rates of disease progression. Rare individuals show no evidence of disease despite greater than ten years of infection. We propose to examine immunological and virological factors which contribute to athe absence of immune attrition in these non-progressors. Subjects will include asymptomatic, untreated adults and adolescents who have had stable and normal CD4 T-cell counts for more than 10 years of HIV-1 infection. Control subjects with progressive disease will be selected for comparison measurements. Phenotypic characterizations of primary viral isolates, biological clones and NL4-3 chimeric clones containing envelope genes from primary isolates will include assays of tropism cytopathogenicity and replication kinetics. Envelope glycoprotein sequences of primary viral isolates will be analyzed and related to these properties. Quantitative cytotoxic T-lymphocyte assays and antibody-dependent cell-mediated cytotoxicity titrations will be performed with targets infected with vaccinia recombinants expressing these same envelope genes. Neutralizing antibody studies will be performed with primary isolates and the chimeric molecular clones. These studies will give us a general picture of how viral phenotype is related to the lack of disease progression and to what extent the envelope glycoprotein defines these properties. By measuring concurrent immunological responses to this viral antigen in the non-progressors and individuals with disease progression. The elements which ar critical for the control of HIV-1 can begin to be defined. The combination of factors that can lead to long-term non-progressive HIV-1 infection will be instructive in the development of therapeutic and prophylactic modalities.
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