HIV MUCOSAL PATHOGENESIS IN PRIMARY INFECTION

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R. Poles' long-term career objective is to become a successful, independent investigator. As a independent investigator, his goal will be to produce funded, investigator-initiated, translational research of high scientific quality. His specific area of interest is the study of pathogenesis of human immunodeficiency virus (HIV) infection in the immune compartment of the gastrointestinal mucosa. This research will enable development of unique and superior methodology for surveillance of HIV patients prior to and during receipt of anti-retroviral agents as well as allowing for development of improved vaccination strategies. In order to achieve his goals, Dr. Poles has designed a three phase career development plan. The initial phase will consist of continuing didactic course work towards a doctoral degree from the Department of Microbiology and Immunology at UCLA. The second phase will be to initiate the research described below under the mentorship of Drs. Irvin Chen and John Walsh. The final phase will involve publication of the study findings and application for independent funding. The first aim of this study is to test the hypothesis that the gastrointestinal mucosa is a fundamental target for HIV in patients with primary infection by quantifying viral load in the tissue with PCR, and showing with flow cytometry and quantitative image analysis the effect of HIV infection on the CD4+ cells in the mucosa. The second aim will examine genotypic differences of virus derived from the blood and mucosa in untreated primary infection patients, and examining the phenotypic expression of these changes. Virus from the two compartments will be compared in terms of replication kinetics and co-receptor usage in co-culture assays. Through this series of experiments, Dr. Poles will attempt to determine the factors responsible for these evolutionary changes. The third aim will use the same techniques as the previous two aims, but specifically examine primary infection patients who have initiated treatment with highly potent antiviral therapy to examine its effects on these parameters.