These studies seek to determine if mutations that alter lentivirus reverse transcriptase fidelity alter pathogenesis by promoting the emergence of drug-resistant and host range viral variants. The studies will employ a model lentivirus (feline immunodeficiency virus - FIV), a single cycle of virus replication (dsDNA -- ssRNA -- dsRNA), and a sensitive cell culture plaque assay to quantify drug-resistant and host range variants. Specifically, the investigators aim to determine the rate of FIV mutation to drug-resistant and host range variants, determine the influence of RT fidelity on mutation rate, and identify FIV mutants with mutator and antimutator phenotypes. Ultimately, interesting FIV variants with altered replication fidelity might be used to infect animals to determine whether alterations in RT fidelity lead to alterations in virulence, patterns of drug resistance or antigenic variation; however, in vivo studies are not part of the current application.
