Infection with the human immune deficiency virus (HIV) is associated with hematologic abnormalities which frequently limit anti-viral, anti-neoplastic and anti-infective therapy. Impaired hematopoiesis appears to be a major cause for anemia and neutropenia in AIDS patients. The focus of this proposal is to further investigate mechanisms for dysregulated hematopoiesis following HIV infection. Specifically we propose to: 1. Evaluate progenitor cell and bone marrow stromal cell infection in vivo using polymerase chain reaction (PCR) analysis of primary patient samples; 2. Infect normal primary stromal cells and an immortalized human bone marrow stromal cell line, BL, with HIV in vitro; 3. Define the functional consequences of HIV infection of marrow stromal cells as measured by a) the support of hematopoiesis in long term bone marrow culture, b) cytokine expression, c) extracellular matrix expression and d) cell surface adhesion molecule expression; 4. Explore the biochemical basis for abnormalities in expression of cellular gene products induced by HIV infection of stroma, and; 5. Verify the role of the altered host gene product in hematopoiesis.
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