FOLLICULAR DENDRITIC CELLS & HIV PATHOGENESIS

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Description (from applicant's abstract): FDC are rare and fragile cells located in germinal centers of lymph nodes. They can retain antigens in their native state for an extended period. The PI previously made a seminal observation that FDC preserves the infectiousness of HIV when mixed with neutralizing antibodies. Based on these observations, the PI presents a hypothesis that FDCs are a dangerous long-term reservoir of infectious HIV and that they provide important and unique contributions to HIV pathogenesis 1) by in vivo maintenance of HIV in an infectious form for many months without viral replication, 2) by potentiating HIV infection/replication; and 3) by permitting HIV infection of target cells in the presence of high concentrations of neutralizing antibody. Specific aims for the new proposal are: 1) To establish the mechanisms used by FDC to protect HIV from the loss of infectivity. 2) To establish the mechanisms used by FDC to potentiate HIV infection/replication by increasing T cell proliferation and by reducing T cell apoptosis. 3) To determine if FDC can archive infectious HIV while being exposed to mutants or new populations of HIV. 4) To determine if the FDC reservoir can be destroyed.