Feline Immunodeficiency Virus, a Model for Potential Rev Function Inhibitors

Prof. Tom Phillips, D.V.M., Ph.D., Associate Dean, Research College of Veterinary Medicine; Western University of Health Sciences; Pomona, CA, U.S.A.

Human immunodeficiency virus type 1 (HIV-1), a lentivirus, is an important human pathogen. HIV-1 does not replicate in the commonly used laboratory animals species. To study the pathogenesis and potential therapeutic approaches, animal lentivirus models have been developed. One of these models is the feline immunodeficiency virus (FIV) of cats. The similarities and difference between the humane and feline viruses will be discussed, with particular emphasis being placed on the Rev regulatory system. Rev regulation is essential for the replication of lentiviruses, including both FIV and HIV-1. Specifically, Rev affects the overall stability of viral mRNAs that encode the necessary structural and enzymatic proteins. The use of FIV, as a model for Rev regulatory system, will be discussed, emphasizing the role of the eukaryotic initiation factor (eIF-5A). eIF-5A is indispensable for Rev function and is the only known protein whose biologically active form requires a unique amino acid, hypusine. Experiments will be described where blocking the formation of hypusine through disrupting the cellular enzyme, deoxyhypusine synthase, altered FIV Rev function, as determined by the effects on viral replication, expression of a Rev-dependent CAT system, and the splicing of viral mRNAs. Through these studies, we believe that FIV/cat system has been established as a small animal model for potential inhibitors that act either directly or indirectly on lentiviral Rev regulation.