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The aim of this proposal is to study the host response to HIV infection by examining the effect of in vivo HIV-1 infection on mononuclear phagocyte antimicrobial and immunoregulatory-immunomodulation functions. In particular, mononuclear phagocyte interactions with Crytococcus neoformans will be studied.
The specific aims are: 1) Does HIV-1 infection of mononuclear phagocytes in vivo affect anticryptococcal function? Functions to be measured include phagocytosis, fungistasis, nitrogen oxidation, oxidative metabolism, cell surface antigen expression. 2) Can HIV-1 infection be demonstrated by reverse transcriptase activity, p24 antigen, immunofluorescence, and in situ hybridization in mononuclear phagocytes from HIV-1 seropositive individuals? 3) Are in vitro mononuclear phagocyte function and clinical stage of HIV-1 infection correlated? 4) Does specific in vivo anti-retroviral therapy decrease HIV-1 infection/latency in mononuclear phagocytes? 5) Does in vivo anti-retroviral therapy improve HIV-1 infected mononuclear phagocyte antimicrobial and immunomodulatory functions? The investigator believes that determing the effect of HIV-1 infection on mononuclear phagocyte-mediated anticryptococcal function will help to understand host-virus interactions, may serve as a marker for disease progression, and could be used as a model for evaluating anti-retroviral therapy.
Cameron, M L; Granger, D L; Matthews, T J et al. (1994) Human immunodeficiency virus (HIV)-infected human blood monocytes and peritoneal macrophages have reduced anticryptococcal activity whereas HIV-infected alveolar macrophages retain normal activity. J Infect Dis 170:60-7 |