ArticleJournal of virology2012
Molecular mechanism of antagonism between the Y181C and E138K mutations in HIV-1 reverse transcriptase.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- A Robust Ensemble Machine Learning Approach for Inhibitor Discovery: Case Study of HIV-1 NNRTI and Validation Using MD Simulation.Chemistry, an Asian journal · 2026Article
- Virulence and Replicative Fitness of HIV-1 Transmitted/Founder (T/F) Viruses Harbouring Drug Resistance-Associated Mutation.Viruses · 2024Article
- Article
- M184I/V substitutions and E138K/M184I/V double substitutions in HIV reverse transcriptase do not significantly affect the antiviral activity of EFdA.The Journal of antimicrobial chemotherapy · 2017Article
- HIV-1 capsid uncoating initiates after the first strand transfer of reverse transcription.Retrovirology · 2016Article
- Drug susceptibility to etravirine and darunavir among Human Immunodeficiency Virus Type 1-derived pseudoviruses in treatment-experienced patients with HIV/AIDS in South Korea.Virology journal · 2015Article
- Review
- Effects of the W153L substitution in HIV reverse transcriptase on viral replication and drug resistance to multiple categories of reverse transcriptase inhibitors.Antimicrobial agents and chemotherapy · 2014Article
- Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China.BMC infectious diseases · 2014Article
- The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity.Journal of virology · 2014Article
- Article
- Role of the K101E substitution in HIV-1 reverse transcriptase in resistance to rilpivirine and other nonnucleoside reverse transcriptase inhibitors.Antimicrobial agents and chemotherapy · 2013Article
- Effect of mutations at position E138 in HIV-1 reverse transcriptase and their interactions with the M184I mutation on defining patterns of resistance to nonnucleoside reverse transcriptase inhibitors rilpivirine and etravirine.Antimicrobial agents and chemotherapy · 2013Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Etravirine (ETR) is an expanded-spectrum nonnucleoside reverse transcriptase inhibitor (NNRTI) approved for use as an antiretroviral agent in treatment-experienced patients. Y181C and E138K in HIV-1 RT are among 20 different drug resistance mutations associated with ETR. However, E138K can be consistently selected by ETR when wild-type viruses but not viruses containing Y181C are grown in tissue culture. This study was carried out to evaluate any possible mechanisms that might explain antagonism between the Y181C and E138K mutations. Accordingly, we performed tissue culture studies to investigate the evolutionary dynamics of E138K in both a wild-type (WT) and a Y181C background. We also generated recombinant enzymes containing Y181C and E138K alone or in combination in order to study enzyme processivity, rates of processive DNA synthesis, enzyme kinetics, and susceptibility to ETR. We now show that the presence of the Y181C mutation prevented the emergence of E138K in cell culture and that the simultaneous presence of E138K and Y181C impaired each of enzyme activity, processivity, rate of processive DNA synthesis, and deoxynucleoside triphosphate (dNTP) affinity. The addition of E138K to Y181C also decreased the level of resistance to ETR compared to that obtained with Y181C alone.
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