The purpose of the proposed research is to develop the feline lentivirus, FIV, as a model for the establishment of intervention therapies to lentivirus infections. The similarities in the life cycle and molecular structure of FIV as well as the immunodeficiency syndrome associated with its infection make findings in this small animal model particularly relevant to treatment of HIV infection in humans. As the smallest of the natural models, FIV is more readily manipulable than primate models. Since FIV is also a problem in veterinary medicine, findings here will be applicable directly to the treatment of a significant disease of cats. The first four years of this study resulted in 1) the molecular cloning and complete nucleotide sequence analysis of two distinct isolates of FIV; 2) the development of immunological reagents to identify nearly all the predicted gene products revealed by the above analyses; 3) identification of spliced messages encoding the Rev equivalent of FIV; 4) identification of a totally new enzyme activity, deoxyuridine triphosphatase, encoded by the pol of gene of FIV; 5) and production of a panel of anti-peptide antibodies and recombinant proteins designed to define the neutralizing epitopes on the FIV Env. We wish now to continue these studies, to 1) further define both B- and T-cell epitopes on the virus; 2) develop recombinant and synthetic immunogens expressing these epitopes; 3) define viral determinants that are responsible for host range differences observed between two unique molecular clones of FIV; 4) further characterize the deoxyuridine triphosphatase (DU) encoded by FIV to determine its relevance and importance to the virus life cycle; and 5) establish whether additional open reading frames in FIV encode proteins. Studies are also underway to molecularly characterize both the reverse transcriptase and aspartate proteinase of FIV with the expressed purpose of developing drug therapies targeted to these enzymes. The program outlined above will allow us to develop fully the FIV model for establishment of efficacious intervention therapies to lentivirus infections.
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