ArticleAntimicrobial agents and chemotherapy2011
Three residues in HIV-1 matrix contribute to protease inhibitor susceptibility and replication capacity.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Contribution of Gag and Protease to HIV-1 Phenotypic Drug Resistance in Pediatric Patients Failing Protease Inhibitor-Based Therapy.Antimicrobial agents and chemotherapy · 2016Trial
- Trial
- HIV-1 envelope facilitates the development of protease inhibitor resistance through acquiring mutations associated with viral entry and immune escape.Frontiers in microbiology · 2024Article
- HIV-1 mutants expressing B cell clonogenic matrix protein p17 variants are increasing their prevalence worldwide.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Article
- HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy.The Journal of antimicrobial chemotherapy · 2020Article
- Reviewing HIV-1 Gag Mutations in Protease Inhibitors Resistance: Insights for Possible Novel Gag Inhibitor Designs.Molecules (Basel, Switzerland) · 2019Review
- Gag-protease coevolution analyses define novel structural surfaces in the HIV-1 matrix and capsid involved in resistance to Protease Inhibitors.Scientific reports · 2017Article
- Inference of Epistatic Effects Leading to Entrenchment and Drug Resistance in HIV-1 Protease.Molecular biology and evolution · 2017Article
- Combination antiretroviral therapy and cell-cell spread of wild-type and drug-resistant human immunodeficiency virus-1.The Journal of general virology · 2017Article
- Wide variation in susceptibility of transmitted/founder HIV-1 subtype C Isolates to protease inhibitors and association with in vitro replication efficiency.Scientific reports · 2016Article
- Transient HIV-1 Gag-protease interactions revealed by paramagnetic NMR suggest origins of compensatory drug resistance mutations.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa.AIDS research and human retroviruses · 2015Article
- Genetic Changes in HIV-1 Gag-Protease Associated with Protease Inhibitor-Based Therapy Failure in Pediatric Patients.AIDS research and human retroviruses · 2015Article
- Viral envelope is a major determinant of enhanced fitness of a multidrug-resistant HIV-1 variant.Journal of acquired immune deficiency syndromes (1999) · 2015Article
- Deep sequencing of protease inhibitor resistant HIV patient isolates reveals patterns of correlated mutations in Gag and protease.PLoS computational biology · 2015Article
- HIV-1 subtype influences susceptibility and response to monotherapy with the protease inhibitor lopinavir/ritonavir.The Journal of antimicrobial chemotherapy · 2015Article
- Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes.The Journal of antimicrobial chemotherapy · 2014Article
- Protease inhibitors effectively block cell-to-cell spread of HIV-1 between T cells.Retrovirology · 2013Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Other than cleavage site mutations, there is little data on specific positions within Gag that impact on HIV protease inhibitor susceptibility. We have recently shown that non-cleavage site mutations in gag, particularly within matrix protein can restore replication capacity and further reduce protease inhibitor drug susceptibility when coexpressed with a drug-resistant (mutant) protease. The matrix protein of this patient-derived virus was studied in order to identify specific changes responsible for this phenotype. Three amino acid changes in matrix (R76K, Y79F, and T81A) had an impact on replication capacity as well as drug susceptibility. Introduction of these three changes into wild-type (WT) matrix resulted in an increase in the replication capacity of the protease mutant virus to a level similar to that achieved by all the changes within the mutant matrix and part of the capsid protein. Pairs of changes to wild-type matrix led to an increased replication capacity of the protease mutant (although less than with all three changes). Having only these three changes to matrix in a wild-type virus (with wild-type protease) resulted in a 5- to 7-fold change in protease inhibitor 50% effective concentration (EC₅₀). Individual changes did not have as great an effect on replication capacity or drug susceptibility, demonstrating an interaction between these positions, also confirmed by sequence covariation analysis. Molecular modeling predicts that each of the three mutations would result in a loss of hydrogen bonds within α-helix-4 of matrix, leading to the hypothesis that more flexibility within this region or altered matrix structure would account for our findings.
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