Infection with human immunodeficiency virus type-I (HIV-1) is complicated by a variety of hematological abnormalities including leukopenia, anemia and thrombocytopenia. Many factors in AIDS patients including active infections, secondary neoplasms, or simultaneous administration of antibiotics and/or cytotoxic drugs can contribute to the severity of this hematopoietic cellular failure. In this application we will attempt to determine, in part, the pathogenesis of the hematopoietic cellular failure in AIDS patients by determining the consequences of HIV-1 infection on both human hematopoietic progenitor cells and stem cells. In addition, the effect of two other viral pathogens, cytomegalovirus (CMV) and the human parvovirus B19 (HPV-B19) on hematopoiesis in AIDS patients will also be examined. As a consequence of the severe immunodeficiency that occurs in AIDS, latent infections with CMV might be reactivated and/or normal host responses to HPV-B19 blunted. Viremia with either of these agents might thus be implicated as contributory factors to hematopoietic suppression in this patient population. To accomplish these goals, we propose to pursue the following specific aims: 1. Determine whether HIV-1 can directly infect human hematopoietic progenitors cells and/or stem cells in vitro. Detect the presence of HIV-1 in marrow elements from AIDS patients. 2. Determine whether autoimmune phenomena in AIDS patients lead to destruction of hematopoietic progenitor cells or stem cells. These autoimmune phenomena might be directed against antigens that are a direct consequence of HIV-1 infection or be due to adsorption of HIV-1 envelope proteins on cell surfaces of progenitor cells. Both of these mechanisms might result in immune clearance or elimination of hematopoietic cells by means of antibody-dependent cytotoxicity. 3. Determine the effect of HPV-B19 and CMV on normal human hematopoietic progenitor cells and stem cells and compare that with the effect of these viruses on similar cell populations obtained from HIV-1 infected patients. Determine whether progenitor cells from AIDS patients are infected with either of these two viruses. The accomplishment of these goals will allow us to further define important components of the multifactorial origin of hematopoietic suppression in AIDS.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL042674-01
Application #
3361014
Study Section
(ARR)
Project Start
1988-12-01
Project End
1993-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
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Klemsz, M; Hromas, R; Raskind, W et al. (1994) PE-1, a novel ETS oncogene family member, localizes to chromosome 1q21-q23. Genomics 20:291-4
Bruno, E; Cooper, R J; Wilson, E L et al. (1993) Basic fibroblast growth factor promotes the proliferation of human megakaryocyte progenitor cells. Blood 82:430-5
Srivastava, A; Bruno, E; Briddell, R et al. (1990) Parvovirus B19-induced perturbation of human megakaryocytopoiesis in vitro. Blood 76:1997-2004