The long-term goal of this project is to determine the mechanisms whereby retroviral infection affects hemopoiesis. A murine model system has been developed in which the WB91-GV retrovirus infects adult mice resulting in immunosuppression and eventually leukemia. WB91-GV is similar to HIV in that it does not express a v-onc gene and it infects adults animals. In these studies the effect of retroviral infection on hemopoiesis will be defined and the temporal relationship of the development of immunodeficiency to altered hemopoiesis will be established. The types of bond marrow cells that are infected by WB91-GV will be determined and the responsiveness of infected cells to GM-CSF, IL3, and combinations of IL3 plus G-CSF, M-CSF or erythropoietin will be assessed. The effect of in vivo treatment of infected animals with GM-CSF in the presence or absence of T lymphocytes will be examined. Diverse technologies ranging from in vivo animal studies to molecular analysis of gene expression will be used. These studies should give us insignt into the effect of retroviral infection on hemopoiesis and should give us experience on how to use exogenous growth factors to reserve some of these effects.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL042090-05
Application #
3360111
Study Section
Special Emphasis Panel (SRC (DB))
Project Start
1988-09-30
Project End
1993-09-29
Budget Start
1992-09-30
Budget End
1993-09-29
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Tumas-Brundage, K M; Garret, W; Blank, K et al. (1996) Murine leukemia virus infects early bone marrow progenitors in immunocompetent mice. Virology 224:573-5
Tumas, K M; Poszgay, J M; Avidan, N et al. (1993) Loss of antigenic epitopes as the result of env gene recombination in retrovirus-induced leukemia in immunocompetent mice. Virology 192:587-95
Tumas, K; Overmoyer, B; Clevenger, C V et al. (1993) Murine leukemia virus infection in immunocompetent adult mice. Virology 192:1-10