Evolutionary Sequence and Structural Basis for the Epistatic Origins of Drug Resistance in HIV.

ABSTRACT: The emergence of drug resistance in the human immunodeficiency virus (HIV) remains a formidable challenge to the long-term efficacy of antiretroviral therapy (ART). A growing body of evidence highlights the critical role of epistasis, the dependence of mutational effects on the sequence context, in shaping the fitness landscape of HIV under ART-induced selection pressure. However, the biophysical origins of the epistatic interactions involved in engendering drug-resistance mutations (DRMs) remain unclear. Are the mutational correlations "intrinsic" to the properties of the protein, or do they arise because of drug binding? We use a Potts sequence-covariation statistical energy model built on patient-derived HIV-1 protein sequences to construct computational double mutant cycles that probe

SUBMITTER: Biswas A 

PROVIDER: S-EPMC12073831 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature