EFFECT OF RETROVIRAL INFECTION ON BONE MARROW

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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.