ROLE OF MONOCYTES IN AIDS AND AS TARGETS FOR ANTIVIRAL THERAPY

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Monocyte-macrophages are important hosts for HIV-1, playing key roles in the dissemination of the virus and the pathogenesis of AIDS. These studies focus on defining altered functions of mononuclear phagocytes from AIDS patients and following HIV-1 infection in vitro. Numerous phenotypic and functional abnormalities have been defined. For example, monocytes in the circulation of normal individuals do not express Fc(gamma)R111, whereas many AIDS monocytes are FC(gamma)RIII positive. Upregulation of this receptor which modulates immunophagocytosis and release of toxic oxygen species may be related to increased circulating levels of TGF-beta. TGF-beta is also a potent immunosuppressive agent and is produced by HIV infected monocytes. Based on the emerging evidence that monocytes are central to the evolution of AIDS, studies are also directed at exploring potential antiviral therapies targeted at the monocyte population. In addition to circulating monocytes, HIV is found in high frequency in tissue macrophages. The gastrointestinal tract is a major route of entry for HIV and a series of studies are focusing on the immunologic and clinical manifestations of HIV infection of the oral cavity and gastrointestinal tract.