Predominance of positive epistasis among drug resistance-associated mutations in HIV-1 protease.

ABSTRACT: Drug-resistant mutations often have deleterious impacts on replication fitness, posing a fitness cost that can only be overcome by compensatory mutations. However, the role of fitness cost in the evolution of drug resistance has often been overlooked in clinical studies or in vitro selection experiments, as these observations only capture the outcome of drug selection. In this study, we systematically profile the fitness landscape of resistance-associated sites in HIV-1 protease using deep mutational scanning. We construct a mutant library covering combinations of mutations at 11 sites in HIV-1 protease, all of which are associated with resistance to protease inhibitors in clinic. Using deep sequencing, we quantify the fitness of thousands of HIV-1 protease mutants after multiple cycles of

SUBMITTER: Zhang TH 

PROVIDER: S-EPMC7605711 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature