Contingency and Entrenchment of Drug-Resistance Mutations in HIV Viral Proteins.

ABSTRACT: The ability of HIV-1 to rapidly mutate leads to antiretroviral therapy (ART) failure among infected patients. Drug-resistance mutations (DRMs), which cause a fitness penalty to intrinsic viral fitness, are compensated by accessory mutations with favorable epistatic interactions which cause an evolutionary trapping effect, but the kinetics of this overall process has not been well characterized. Here, using a Potts Hamiltonian model describing epistasis combined with kinetic Monte Carlo simulations of evolutionary trajectories, we explore how epistasis modulates the evolutionary dynamics of HIV DRMs. We show how the occurrence of a drug-resistance mutation is contingent on favorable epistatic interactions with many other residues of the sequence background and that subsequent mutations entr

SUBMITTER: Choudhuri I 

PROVIDER: S-EPMC9841799 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature