Infection with Human Immunodeficiency Virus (HIV) results in several important pathologic manifestations. The most apparent and perhaps the best studied are its devastating effects on the immune and the central nervous systems (CNS). Although progress has been made on determining the mechanisms of lymphopenia, the proximate cause of immune deficiency, dysregulation of other bone marrow derived lineages is poorly understood. The development of a simian model of AIDS permits us to study pathogenesis in the laboratory environment. Important variables such as virus strain, dose, route and time of infections will be experimentally controlled. The expertise provided by the other participating investigators will allow us to correlate our findings with neuropathologic data, a third important pathologic manifestation. The primary objectives of this project, therefore, are: 1) to characterize the changes in bone marrow organization and function that occur following Simian Immunodeficiency Virus (SIV) infection of Rhesus monkeys, 2) to assess immunopathogenesis in infected animals, 3) to determine the effects of viral infection on progenitor growth, differentiation, and growth factor production and, 4) identify progenitor populations susceptible to viral infection using neurotropic and non-neurotropic strains. These studies will be conducted using tissues from experimentally infected animals as well as in vitro infected material from healthy animals. From the proposed studies we hope to gain a better understanding of the mechanisms of SIV/HIV induced dysregulation of bone marrow function and correlate these changes with CNS disease and immune deficiency.
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