MOUSE MODEL FOR RETROVIRUS INDUCTION OF IMMUNODEFICIENCY

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The objectives of our proposed studies are to understand how a model retrovirus infection of mice leads to profound immunodeficiency disease, to evlauate the interaction of other infectious agents with the retrovirus in the induction of immunodeficiency, and to document that his murine disease is an accurate and useful model for acquired immunodeficiency syndrome (AIDS). The retrovirus that causes murine AIDS is a mixture of ecotropic and mink cell focus-forming murine leukemia viruses termed LP-BM 5 MuLV. Infection of susceptible strains of mice with LP-BM 5 MuLV leads to the rapid and reproducible loss of both cellular and humoral immunity. Athymic nude mice are resistant to most effects of LP-BM 5 MuLV infection. Our specific aims are to determine the role of T lymphocytes in disease induction, to examine the causes of the polyclonal B cell activation that is a prominent feature of the disease, to study altered macrophage function during LP-BM 5 MuLV infection, to investigate overproduction of lymphokines during the disease, and to seek evidence of autoimmune phenomena contributing to the rapid loss of immune function. In addition, we will investigate the interaction of LP-BM 5 MuLV infection and several opportunistic infections common in AIDS patients. These experimental infectious agents include herpes simplex I, murine cytomegalovirus, Candida albicans, and Salmonella dublin. These studies will examine both increased susceptibility to these opportunistic pathogens following LP-BM 5 MuLV infection and acceleration of murine AIDS by co-infection with one or more of these agents and LP-BM 5 MuLV. Therapeutic intervention in ongoing murine AIDs with cyclosporin A will be investigated in an attempt to develop a strategy for treating AIDS patients.