Kinetic coevolutionary models predict the temporal emergence of HIV-1 resistance mutations under drug selection pressure.

ABSTRACT: Drug resistance in HIV type 1 (HIV-1) is a pervasive problem that affects the lives of millions of people worldwide. Although records of drug-resistant mutations (DRMs) have been extensively tabulated within public repositories, our understanding of the evolutionary kinetics of DRMs and how they evolve together remains limited. Epistasis, the interaction between a DRM and other residues in HIV-1 protein sequences, is key to the temporal evolution of drug resistance. We use a Potts sequence-covariation statistical-energy model of HIV-1 protein fitness under drug selection pressure, which captures epistatic interactions between all positions, combined with kinetic Monte-Carlo simulations of sequence evolutionary trajectories, to explore the acquisition of DRMs as they arise in an ensemble of

SUBMITTER: Biswas A 

PROVIDER: S-EPMC11009627 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature