The overall goal of this project is to determine the molecular mechanisms by which feline immunodeficiency virus (FIV) injures feline T4 cells and to determine whether cytopathology is influenced by concomitant infection with cytotoxic or noncytotoxic FeLV strains.
We aim to determine the similarities and differences between feline lentivirus-induced immunodeficiency and HIV on one hand, and with FeLV-induced cytopathology on the other hand, so that a basis will be established to determine the usefulness of the FIV system as a therapeutic model of HIV infection. Since the overall focus of this program is to understand the molecular mechanisms of cytopathology of HIV with the goal of targeting those processes for rational drug design, we will examine in this project aspects of FIV infection which are relevant to cytopathology.
Our specific aims are to: 1) determine whether cytotoxic FIV infection leads to alterations in host lipid metabolism, macromolecular synthesis, intracellular calcium balance, membrane permeability, and cell-cycle kinetics; 2) determine whether cytotoxic FIV infection leads to alterations in expression of feline lymphocyte genes; 3) determine whether FIV infection triggers apoptosis in feline T4 cells; and 4) determine whether FIV, exogenous FeLV, and endogenous FeLV interact and whether this interaction influences cytopathology.
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