ArticleThe Journal of biological chemistry2010
N348I in HIV-1 reverse transcriptase can counteract the nevirapine-mediated bias toward RNase H cleavage during plus-strand initiation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Frequent emergence of N348I in HIV-1 subtype C reverse transcriptase with failure of initial therapy reduces susceptibility to reverse-transcriptase inhibitors.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2012Trial
- Evaluation of a Novel In-house HIV-1 Genotype Drug Resistance Assay using Clinical Samples in China.Current HIV research · 2022Article
- INSTIs and NNRTIs Potently Inhibit HIV-1 Polypurine Tract Mutants in a Single Round Infection Assay.Viruses · 2021Article
- Mutations in the HIV-1 3'-Polypurine Tract and Integrase Strand Transfer Inhibitor Resistance.Antimicrobial agents and chemotherapy · 2021Article
- Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction.Viruses · 2021Article
- Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis.Nucleic acids research · 2015Article
- Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations.Proteins · 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
- 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
- N348I in HIV-1 reverse transcriptase counteracts the synergy between zidovudine and nevirapine.Journal of acquired immune deficiency syndromes (1999) · 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
- Global Conformational Dynamics of HIV-1 Reverse Transcriptase Bound to Non-Nucleoside Inhibitors.Biology · 2012Article
- Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China.PloS one · 2012Article
- Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase.Retrovirology · 2011Article
- Article
- Impact of the N348I mutation in HIV-1 reverse transcriptase on nonnucleoside reverse transcriptase inhibitor resistance in non-subtype B HIV-1.Antimicrobial agents and chemotherapy · 2011Article
- The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase decreases binding to nevirapine.The Journal of biological chemistry · 2010Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Drug resistance-associated mutations in HIV-1 reverse transcriptase (RT) can affect the balance between polymerase and ribonuclease H (RNase H) activities of the enzyme. We have recently demonstrated that the N348I mutation in the connection domain causes selective dissociation from RNase H-competent complexes, whereas the functional integrity of the polymerase-competent complex remains largely unaffected. N348I has been associated with resistance to the non-nucleoside RT inhibitor (NNRTI), nevirapine; however, a possible mechanism that links changes in RNase H activity to changes in NNRTI susceptibility remains to be established. To address this problem, we consider recent findings suggesting that NNRTIs may affect the orientation of RT on its nucleic acid substrate and increase RNase H activity. Here we demonstrate that RNase H-mediated primer removal is indeed more efficient in the presence of NNRTIs; however, the N348I mutant enzyme is able to counteract this effect. Efavirenz, a tight binding inhibitor, restricts the influence of the mutation. These findings provide strong evidence to suggest that N348I can thwart the inhibitory effects of nevirapine during initiation of (+)-strand DNA synthesis, which provides a novel mechanism for resistance. The data are in agreement with clinical data, which demonstrate a stronger effect of N348I on susceptibility to nevirapine as compared with efavirenz.
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