This proposal describes a 3-year training program for the development of an academic career in Infectious Diseases. The principal investigator has successfully completed the first year in the Infectious Diseases fellowship program at UCLA Medical Center and is ready to expand his scientific skills. The applicant has had a successful background in biochemistry and molecular biology, however he would benefit from additional training in virology and immunology to ultimately prepare him for a career in viral pathogenesis research. The Division of Infectious Diseases at UCLA Medical Center is part of the STAR Fellowship Program, a unique program committed to training physicians in subspecialty medicine for careers in basic research. It is an ideal environment to pursue a career in academic medicine. Research will center on understanding the immunologic factors regulating HIV latency. This project will be mentored by Dr. Jerry Zack, a recognized leader in HIV pathogenesis and HIV latency and associate director of basic sciences at the UCLA AIDS Institute. In addition, two consultants, Dr. Otto Yang and Dr. Derya Unutmaz, have been enlisted to provide advice and facilitate training of the principal investigator. Specifically, the research plan will determine the role of T regulatory cells in modulating latent HIV infection. Given that T regulatory cells can suppress the proliferation and effector functions of activated T cells, we hypothesize that they may also inhibit activation of latent HIV infection. To this end, we have developed an in vitro assay for studying HIV latency in primary cells, as well as a convenient method for deriving significant numbers of T regulatory cells. We will use these methods to determine the ability of T regulatory cells to suppress activation of latent HIV infection and to explore possible mechanisms of suppression. We will also extend these studies by isolating and expanding both non-specific and HIV-specific T regulatory cells from patients infected with HIV and testing their ability to inhibit activation of latent infection. Anti-retroviral drugs must be taken for life in patients infected with HIV because a portion of the virus lies latent and hidden from the effects of anti-HIV medications. This proposal outlines experiments to determine how HIV remains latent, and therefore it has important clinical implications if cure of HIV is to be ultimately be achieved.
