In vitro characterization of FIV-pPPR, a pathogenic molecular clone of feline immunodeficiency virus, and two drug-resistant pol gene mutants

—To compare in vitro replication kinetics and nucleoside analog susceptibilities of a natural feline immunodeficiency virus (FIV) isolate (FIV-Maxam), a molecular clone of FIV (FIV-pPPR), and two (-)-β-L-2',3'-dideoxy-3'-thiacytidine- (3TC-) resistant mutants of FIV-pPPR. —Peripheral blood mononuclear cells (PBMC) from 4 specific-pathogenfree cats. —Two point mutations corresponding to mutations of human immunodeficiency virus type 1 (HIV-1) were engineered into the highly conserved YMDD motif of the reverse transcriptase- (RT-) encoding region of the FIV-pPPR gene. Replication kinetics and nucleoside analog susceptibilities of FIV-Maxam, FIV-pPPR, and the 2 mutant viruses were measured in vitro, using feline PBMC. —Replication kinetics and nucleoside analog susceptibilities were similar between FIV-Maxam and FIV-pPPR. However, FIV-Maxam was significantly more susceptible to 3TC. A methionine-to-valine mutation at codon 183 (M183V) of the RT-encoding region of the gene of FIV-pPPR conferred highlevel phenotypic resistance to 3TC and cross-resistance to the related compound (-)-β-L-2',3'-dideoxy-5- fluoro-3'-thiacytidine. —Similarities between FIV-Maxam and FIV-pPPR suggest that results of studies performed using FIV-pPPR will have relevance to natural FIV infection in cats. In vitro evaluation of nucleoside analog susceptibilities of FIV-Maxam may help determine concentrations of nucleoside analogs required for effective treatment of FIV-infected cats. —3TC resistance of FIV-pPPR M183V was similar in magnitude to that of HIV-1 M184V, a mutant described in infected humans treated with 3TC. Thus, FIV-pPPR M183V may be a useful model for studying the in vivo effects of 3TC resistance on lentivirus pathogenesis. ( 2001;62:588–594)

Duke Scholars

Author Mary Ann McCrackin Pathology