A systems analysis of mutational effects in HIV-1 protease and reverse transcriptase
Related Experiment Video
Updated: Jun 3, 2026

Amplification of Near Full-length HIV-1 Proviruses for Next-Generation Sequencing
Published on: October 16, 2018
Trevor Hinkley1, João Martins, Colombe Chappey
1ETH Zürich, Institute of Integrative Biology, Zürich, Switzerland.
Abstract:
The development of a quantitative understanding of viral evolution and the fitness landscape in HIV-1 drug resistance is a formidable challenge given the large number of available drugs and drug resistance mutations. We analyzed a dataset measuring the in vitro fitness of 70,081 virus samples isolated from HIV-1 subtype B infected individuals undergoing routine drug resistance testing. We assayed virus samples for in vitro replicative capacity in the absence of drugs as well as in the presence of 15 individual drugs. We employed a generalized kernel ridge regression to estimate main fitness effects and epistatic interactions of 1,859 single amino acid variants found within the HIV-1 protease and reverse transcriptase sequences. Models including epistatic interactions predict an average of 54.8% of the variance in replicative capacity across the 16 different environments and substantially outperform models based on main fitness effects only. We find that the fitness landscape of HIV-1 protease and reverse transcriptase is characterized by strong epistasis.
More Related Videos
14:23A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
Published on: August 31, 2014
10:29Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Related Concept Videos
Viral Mutations
Inhibitors of Virion Maturation and Assembly
Retrovirus Life Cycles