Altered Gag Polyprotein Cleavage Specificity of Feline Immunodeficiency Virus/Human Immunodeficiency Virus Mutant Proteases as Demonstrated in a Cell-Based Expression System

摘要: We have used feline immunodeficiency virus (FIV) protease (PR) as a mutational system to study the molecular basis of substrate-inhibitor specificity for lentivirus PRs, with focus on human type 1 (HIV-1) PR. Our previous mutagenesis studies demonstrated that discrete substitutions in active site FIV PR structurally equivalent residues HIV-1 dramatically altered mutant PRs vitro analyses. Here, we expanded these analyze changes each expressed context natural Gag-Pol polyprotein ex vivo. Expression mutants were prepared which 4 12 HIV-1-equivalent made PR, and cleavage was then assessed pseudovirions from transduced cells. The findings that, analyses, inhibitor specificities showed increased character when analyzed against substrate. In addition, all still processed but apparent order processing relative observed wild-type Given importance is processed, likely explain failure produce infectious FIVs bearing mutations.