The goal of the proposed research is to further define the molecular properties of FIV, because FIV infection in cats is a valuable and manipulable model for HIV. Previous work under this application has resulted in 1) the complete nucleotide sequence of two distinct isolates of FIV; 2) development of immunological reagents and probes against most of the major viral gene products, feline cytokines and cell surface markers; 3) definition of the structural genes of gag and the enzyme cassette encoded by pol; 4) identification of the major spliced messages encoded by the virus; 5) identification of Rev and the RRE; 6) definition and characterization of the unique enzyme, deoxyuridine triphosphatase (DU), encoded within pol of FIV; 7) preparation and analysis of DU FIV and test of its replication in vivo; 8) identification of an apparent transactivating protein, Orf 2, necessary for efficient growth in primary T cells and macrophages; and 9) studies to define regions of envelope that facilitate entry of the virus into the host cell. This application is for continuation of these studies to further characterize the system as follows: 1) further characterize DU to define its role in the virus life cycle and to complete the identification of the active site of the enzyme; 2) examine the expression of the Orf 2 gene product in virus-infected cells; localize the expression of the cells; 3) further define the molecular character of Env and investigate the mechanism of an apparent block to virus egress facilitated by an antibody to the cell surface marker, CD9; 4) identify any additional gene products that may be encoded by the FIV genome, potential 11.3 kDa protein encoded by a short open reading frame in the minus strand of the integrated provirus; and 5) continue collaborative studies to develop a FIV/HIV chimeric to facilitate the direct testing of antivirals specific for HIV RT testable animal system. These studies will further define the molecular character of FIV as well as establish the differences and similarities between the cat and human lentivirus systems.
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