ArticleJournal of virology2007
Mutations in human immunodeficiency virus type 1 RNase H primer grip enhance 3'-azido-3'-deoxythymidine resistance.
Article in Journal of virology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 77 citations in OpenAlex.
- Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase.PloS one · 2012Trial
- Reverse Transcriptase Connection and RNase H Domain Variation in HIV-1 Subtype C Among Individuals with Virologic Failure in Botswana.Biomedicines · 2026Article
- Characterisation of RT Connection and RNase H Polymorphisms in HIV-1 Subtype C in Botswana.Viruses · 2026Article
- Nucleocapsid Protein Precursors NCp9 and NCp15 Suppress ATP-Mediated Rescue of AZT-Terminated Primers by HIV-1 Reverse Transcriptase.Antimicrobial agents and chemotherapy · 2020Article
- Article
- Structural Maturation of HIV-1 Reverse Transcriptase-A Metamorphic Solution to Genomic Instability.Viruses · 2016Review
- Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis.Nucleic acids research · 2015Article
- AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase.Retrovirology · 2015Article
- Molecular mechanism of HIV-1 resistance to 3'-azido-2',3'-dideoxyguanosine.Antiviral research · 2014Article
- From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir.Current pharmaceutical design · 2013Review
- Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant.Cellular and molecular biology (Noisy-le-Grand, France) · 2012Article
- HIV-1 reverse transcriptase (RT) polymorphism 172K suppresses the effect of clinically relevant drug resistance mutations to both nucleoside and non-nucleoside RT inhibitors.The Journal of biological chemistry · 2012Article
- Article
- The Impact of HIV Genetic Polymorphisms and Subtype Differences on the Occurrence of Resistance to Antiretroviral Drugs.Molecular biology international · 2012Article
- HIV-1 Reverse Transcriptase Still Remains a New Drug Target: Structure, Function, Classical Inhibitors, and New Inhibitors with Innovative Mechanisms of Actions.Molecular biology international · 2012Article
- Review
- Connection domain mutations in HIV-1 reverse transcriptase do not impact etravirine susceptibility and virologic responses to etravirine-containing regimens.Antimicrobial agents and chemotherapy · 2011Article
- The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains.Retrovirology · 2011Article
- Clinical management of HIV drug resistance.Viruses · 2011Review
- Phenotypic characterization of drug resistance-associated mutations in HIV-1 RT connection and RNase H domains and their correlation with thymidine analogue mutations.The Journal of antimicrobial chemotherapy · 2011Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
We recently observed that mutations in the human immunodeficiency type 1 (HIV-1) reverse transcriptase (RT) connection domain significantly increase 3'-azido-3'-deoxythymidine (AZT) resistance up to 536 times over wild-type (WT) RT in the presence of thymidine analog resistance mutations (TAMs). These mutations also decreased RT template switching, suggesting that they altered the balance between nucleotide excision and template RNA degradation, which in turn increased AZT resistance. Several residues in the HIV-1 connection domain contact the primer strand and form an RNase H primer grip structure that helps to position the primer-template at the RNase H and polymerase active sites. To test the hypothesis that connection domain mutations enhanced AZT resistance by influencing the RNase H primer grip, we determined the effects of alanine substitutions in RNase H primer grip residues on nucleoside RT inhibitor resistance in the context of a WT, TAM-containing, or K65R-containing polymerase domain. Ten of the 11 RNase H primer grip mutations increased AZT resistance 20 to 243 times above WT levels in the context of a TAM-containing polymerase domain. Furthermore, all mutations in the RNase H primer grip decreased template switching, suggesting that they reduced RNase H activity. These results demonstrate that mutations in the RNase H primer grip region can significantly enhance AZT resistance and support the hypothesis that mutations in the connection and RNase H domains can increase resistance by altering the RNase H primer grip region, changing interactions between RT and the template-primer complex and/or shifting the balance between the polymerase and RNase H activities.
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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.