ArticlePLoS computational biology2015
Deep sequencing of protease inhibitor resistant HIV patient isolates reveals patterns of correlated mutations in Gag and protease.
Article in PLoS computational biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016Pooled it
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- Algorithms for Short-Read Viral Haplotype Reconstruction: Challenges, Solutions, and Perspectives.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Efficient epistasis inference via higher-order covariance matrix factorization.bioRxiv : the preprint server for biology · 2024Article
- Kinetic coevolutionary models predict the temporal emergence of HIV-1 resistance mutations under drug selection pressure.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- ViReMa: a virus recombination mapper of next-generation sequencing data characterizes diverse recombinant viral nucleic acids.GigaScience · 2023Article
- Parallel evolution and enhanced virulence uponVirus evolution · 2023Article
- Contingency and Entrenchment of Drug-Resistance Mutations in HIV Viral Proteins.The journal of physical chemistry. B · 2022Article
- Protease and gag diversity and drug resistance mutations among treatment-naive Mexican people living with HIV.BMC infectious diseases · 2022Article
- Covariation of viral recombination with single nucleotide variants during virus evolution revealed by CoVaMa.Nucleic acids research · 2022Article
- Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients.Scientific reports · 2022Article
- Article
- MrHAMER yields highly accurate single molecule viral sequences enabling analysis of intra-host evolution.Nucleic acids research · 2021Article
- Epidemiological data analysis of viral quasispecies in the next-generation sequencing era.Briefings in bioinformatics · 2021Review
- Predominance of positive epistasis among drug resistance-associated mutations in HIV-1 protease.PLoS genetics · 2020Article
- HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy.The Journal of antimicrobial chemotherapy · 2020Article
- Article
- Reviewing HIV-1 Gag Mutations in Protease Inhibitors Resistance: Insights for Possible Novel Gag Inhibitor Designs.Molecules (Basel, Switzerland) · 2019Review
- Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance.Biochemistry · 2019Article
- Neutral Theory and Rapidly Evolving Viral Pathogens.Molecular biology and evolution · 2018Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
While the role of drug resistance mutations in HIV protease has been studied comprehensively, mutations in its substrate, Gag, have not been extensively cataloged. Using deep sequencing, we analyzed a unique collection of longitudinal viral samples from 93 patients who have been treated with therapies containing protease inhibitors (PIs). Due to the high sequence coverage within each sample, the frequencies of mutations at individual positions were calculated with high precision. We used this information to characterize the variability in the Gag polyprotein and its effects on PI-therapy outcomes. To examine covariation of mutations between two different sites using deep sequencing data, we developed an approach to estimate the tight bounds on the two-site bivariate probabilities in each viral sample, and the mutual information between pairs of positions based on all the bounds. Utilizing the new methodology we found that mutations in the matrix and p6 proteins contribute to continued therapy failure and have a major role in the network of strongly correlated mutations in the Gag polyprotein, as well as between Gag and protease. Although covariation is not direct evidence of structural propensities, we found the strongest correlations between residues on capsid and matrix of the same Gag protein were often due to structural proximity. This suggests that some of the strongest inter-protein Gag correlations are the result of structural proximity. Moreover, the strong covariation between residues in matrix and capsid at the N-terminus with p1 and p6 at the C-terminus is consistent with residue-residue contacts between these proteins at some point in the viral life cycle.
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Registered trials
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