The objectives of this proposal are to study: 1. The relationship between CD-4 Internalization and susceptibility to HIV-1 Infection. We transfected the human CD-4 gene into murine T cell hybridomas, one of these hybridomas can be infected by HIV-1. The cell biology of the CD-4 molecules will be studied with particular emphasis on the mechanism of CD-4 internalization. The relationship between the capacity of the T cell hybridomas to internalize CD-4 molecules and their sensitivity to HIV-1 infection will be investigated. We will investigate the effects of HIV-1 infection on the activation of CD-4 bearing T cell hybridomas. 2. Effects of HIV-1 gene expression on the physiology of lymphocytes and monocytes. We transfected the tatIII gene of HIV- l into a murine B cell lymphoma (A20), a murine antigen specific T cell hybridoma (7E2) and a murine monocyte tumor line (P388D1). These cell lines were chosen because their surface antigens, antigen specificities, and antibody and lymphokine production have been well characterized. In addition, these cell types are similar to the cell types known to be infected by HIV-l, T cells, monocytes and some B cells. We will continue to study the effects of the tatIII gene on the expression of surface antigens and the physiology of these transfected cell lines. 3. Immune responses against HIV-l encoded antigens in mice. We have immunized normal mice with tatIII transfected cell lines and generated antigen specific CTL and polyclonal antisera specific for tatIII transfected cell lines. The epitopes that are essential for the elicitation of CTL will be identified. We plan to characterize the new proteins induced by the tatIII gene. The results from these experiments should provide useful insights into the mode of action of the tatIII gene and the immune responses against tatIII gene products. We plan to immunize mice with HIV- l infected murine cell lines and study T cell mediated and humoral immune responses to HIV-l infected cells in vivo. These investigations utilize in vivo and in vitro models of HIV-l infection in the murine system. These model systems are designed to facilitate discovery of the mechanisms of HIV-l entry into host cells and the effects of HIV-l gene expression on cell physiology and function. By studying the immune response to murine cell lines either transfected with individual genes or infected with HIV-l, we will be studying the mode of action of individual viral genes and the host immune responses against HIV-l. These experiments will provide fundamental insights into the pathogenesis of HIV-l infection.
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