ArticleJournal of virology2010
Divergent evolution in reverse transcriptase (RT) of HIV-1 group O and M lineages: impact on structure, fitness, and sensitivity to nonnucleoside RT inhibitors.
Article in Journal of virology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- HIV-1 Non-Group M Strains and ART.Viruses · 2023Review
- Structure-based non-nucleoside inhibitor design: Developing inhibitors that are effective against resistant mutants.Chemical biology & drug design · 2021Article
- Long-Acting Anti-HIV Drugs Targeting HIV-1 Reverse Transcriptase and Integrase.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Multiple HIV-1/M + HIV-1/O dual infections and new HIV-1/MO inter-group recombinant forms detected in Cameroon.Retrovirology · 2017Article
- Characterization and in vitro activity of a branched peptide boronic acid that interacts with HIV-1 RRE RNA.Bioorganic & medicinal chemistry · 2016Article
- HIV-1 Group O Genotypes and Phenotypes: Relationship to Fitness and Susceptibility to Antiretroviral Drugs.AIDS research and human retroviruses · 2016Article
- Effect of intercalator and Lewis acid-base branched peptide complex formation: boosting affinity towards HIV-1 RRE RNA.MedChemComm · 2016Article
- The Two-Phase Emergence of Non Pandemic HIV-1 Group O in Cameroon.PLoS pathogens · 2015Article
- Long-term control of viral replication in a Group O, human immunodeficiency virus type 1-infected individual.AIDS research and human retroviruses · 2014Article
- Article
- In vitro and in vivo activities of AIC292, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor.Antimicrobial agents and chemotherapy · 2013Article
- Non-M variants of human immunodeficiency virus type 1.Clinical microbiology reviews · 2013Review
- Multifaceted mechanisms of HIV inhibition and resistance to CCR5 inhibitors PSC-RANTES and Maraviroc.Antimicrobial agents and chemotherapy · 2013Article
- HIV-1 resistance to maraviroc conferred by a CD4 binding site mutation in the envelope glycoprotein gp120.Journal of virology · 2013Article
- Article
- Viral fitness: definitions, measurement, and current insights.Current opinion in virology · 2012Review
- Effect of natural polymorphisms in the HIV-1 CRF02_AG protease on protease inhibitor hypersusceptibility.Antimicrobial agents and chemotherapy · 2012Article
- HIV-1 antiretroviral drug therapy.Cold Spring Harbor perspectives in medicine · 2012Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Natural evolution in primate lentiviral reverse transcriptase (RT) appears to have been constrained by the necessity to maintain function within an asymmetric protein composed of two identical primary amino acid sequences (66 kDa), of which one is cleaved (51 kDa). In this study, a detailed phylogenetic analysis now segregates groups O and M into clusters based on a cysteine or tyrosine residue located at position 181 of RT and linked to other signature residues. Divergent evolution of two group O (C181 or Y181) and the main (Y181 only) HIV-1 lineages did not appreciably impact RT activity or function. Group O RT structural models, based on group M subtype B RT crystal structures, revealed that most evolutionarily linked amino acids appear on a surface-exposed region of one subunit while in a noncatalytic RT pocket of the other subunit. This pocket binds nonnucleoside RT inhibitors (NNRTI); therefore, NNRTI sensitivity was used to probe enzyme differences in these group O and M lineages. In contrast to observations showing acquired drug resistance associated with fitness loss, the C181Y mutation in the C181 group O lineage resulted in a loss of intrinsic NNRTI resistance and was accompanied by fitness loss. Other mutations linked to the NNRTI-resistant C181 lineage also resulted in altered NNRTI sensitivity and a net fitness cost. Based on RT asymmetry and conservation of the intricate reverse transcription process, millions of years of divergent primate lentivirus evolution may be constrained to discrete mutations that appear primarily in the nonfunctional, solvent-accessible NNRTI binding pocket.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.