It has been hypothesized that some hematologic abnormalities in AIDS patients could be caused by disruption of stem/progenitor cell function as the result of dysregulated stromal cell supporting functions following their infection with HIV-1. Alternatively, it has been hypothesized that these abnormalities could be the result of viral products, T cell/macrophage cytokines, or direct viral infection of stem/progenitor cells. HIV-1-induced pathologic changes in stromal cells and stem/progenitor cells will be modeled by two different, but complementary means: (i) by long-term culture (LTC) and high proliferative potential colony forming cell (HPP-CFC) system; and (ii) by using a novel small animal model created by engrafting human stromal cells and CD34+ cells in neonatal SCID (hu-nSCID) mice. The specific goals of this proposed study are: (i) to determine whether the cellular tropic and cytopathic characteristics of distinct HIV-1 isolates effects the ability of stromal cells to provide support for """"""""long-term culture initiating cells"""""""" (LTC-IC) of bone marrow; (ii) to investigate whether the cellular tropic and cytopathic characteristics of distinct HIV-1 isolates allows for infection and death of hematopoietic stem/progenitor cells; and (iii) to utilize human CD34/stromal cell-engrafted SCID mice to study HIV-1 infection.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Special Emphasis Panel (ZHL1-CSR-C (S1))
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Badman, David G
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Scripps Research Institute
La Jolla
United States
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