The overall goal of this project is to determine how cytopathic strains of FeLV damage feline T4 lymphoid cells. This goal and this project parallel those of the HIV work in this program, which aim to understand the molecular mechanisms of HIV cytopathology in order to target those processes for rational drug design. Our rationale is that, if we understand the similarities and differences between the pathogenic mechanisms of FeLV and HIV, then we will know which aspects of FeLV-induced immunosuppression may be accurate models of HIV-induced immunosuppression. This would provide the basis to eventually use FAIDS as an in vivo model for testing therapeutic agents countering the process of HIV cytopathology. The studies proposed continue the work initiated during the initial NCDDG funding, addressing the next questions which were generated during those studies.
Our specific aims are to: 1) determine the mechanism by which FeLV-C induces programmed cell death (apoptosis) in feline T4 cells, 2) determine whether cytotoxic infection with FeLV-C alters expression of endogenous FeLV sequences in feline T4 cells, 3) determine the mechanism by which cytopathic infection with FeLV-C leads to alterations in cellular lipid metabolism, 4) determine which genetic sequences of FeLV-C influence cytopathology, and 5) determine whether therapeutic agents that prevent or delay apoptosis or alter expression of feline lymphocyte genes will ameliorate cytopathology of FeLV-C for feline T4 cells.
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