ArticleJournal of virology2009
The human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor resistance mutation I132M confers hypersensitivity to nucleoside analogs.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Discovery of Novel Amino Acids (Analogues)-Substituted Thiophene[3,2-International journal of molecular sciences · 2024Article
- The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design.Drug design, development and therapy · 2021Review
- Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs.Journal of virology · 2019Article
- Identification of Structural and Molecular Features Involved in the Transport of 3'-Deoxy-Nucleoside Analogs by Human Equilibrative Nucleoside Transporter 3.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- In silico target fishing and pharmacological profiling for the isoquinoline alkaloids of Macleaya cordata (Bo Luo Hui).Chinese medicine · 2015Article
- Competitive fitness assays indicate that the E138A substitution in HIV-1 reverse transcriptase decreases in vitro susceptibility to emtricitabine.Antimicrobial agents and chemotherapy · 2014Article
- 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
- Molecular mechanism of antagonism between the Y181C and E138K mutations in HIV-1 reverse transcriptase.Journal of virology · 2012Article
- Compensation by the E138K mutation in HIV-1 reverse transcriptase for deficits in viral replication capacity and enzyme processivity associated with the M184I/V mutations.Journal of virology · 2011Article
- Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase.Retrovirology · 2011Article
- Clinical management of HIV drug resistance.Viruses · 2011Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
We previously identified a rare mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), I132M, which confers high-level resistance to the nonnucleoside RT inhibitors (NNRTIs) nevirapine and delavirdine. In this study, we have further characterized the role of this mutation in viral replication capacity and in resistance to other RT inhibitors. Surprisingly, our data show that I132M confers marked hypersusceptibility to the nucleoside analogs lamivudine (3TC) and tenofovir at both the virus and enzyme levels. Subunit-selective mutagenesis studies revealed that the mutation in the p51 subunit of RT was responsible for the increased sensitivity to the drugs, and transient kinetic analyses showed that this hypersusceptibility was due to I132M decreasing the enzyme's affinity for the natural dCTP substrate but increasing its affinity for 3TC-triphosphate. Furthermore, the replication capacity of HIV-1 containing I132M is severely impaired. This decrease in viral replication capacity could be partially or completely compensated for by the A62V or L214I mutation, respectively. Taken together, these results help to explain the infrequent selection of I132M in patients for whom NNRTI regimens are failing and furthermore demonstrate that a single mutation outside of the polymerase active site and inside of the p51 subunit of RT can significantly influence nucleotide selectivity.
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