This proposal stems from our previous studies examining molecular mechanisms by which HIV and FeLV injure cells. Our studies on FeLV have implicated the viral envelope glycoprotein in cell injury, as have others with HIV, and our work has indicated that HIV perturbs cellular membrane functions, causing influx of ions, and shutdown of phospholipid synthesis. Based on these results, we have begun preliminary studies of methods to counter the biochemical insults induced by HIV, and have found that agents which enhance phospholipid synthesis act to protect the infected cell. We feel that development of such a therapy which acts to heal or protect the infected cell rather than to cripple the virus may be useful clinically. Such a therapy used in combination with antiviral agents could potentially prove to be very beneficial to AIDS patients.
The aims of this proposal are to continue our basic studies on how HIV injure cells, focusing on examining enzymatic steps and ribonucleotide levels important in the lipid biosynthetic pathways, to test in HIV cytotoxicity and immunosuppression assays in vitro candidate therapeutic compounds which may reduce cellular membrane damage and/or enhance phospholipid synthesis, and to perform parallel studies with FeLV cytotoxicity and immunosuppression in vitro to determine if the same biochemical lesions occur in that system, and if so, if the compounds protect (as a prelude to in vivo testing in cats).
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