ArticleJournal of virology2010
Reduced fitness in cell culture of HIV-1 with nonnucleoside reverse transcriptase inhibitor-resistant mutations correlates with relative levels of reverse transcriptase content and RNase H activity in virions.
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 29 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis.The Lancet. Infectious diseases · 2018Pooled it
- Characterizing HIV drug resistance in cases of vertical transmission in the VESTED randomized antiretroviral treatment trial.Journal of acquired immune deficiency syndromes (1999) · 2024Trial
- Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection.PloS one · 2011Trial
- Recombinant Forms of HIV-1 in the Last Decade of the Epidemic in the Russian Federation.Viruses · 2023Article
- Premature Stop Codon at Residue 101 within HIV-1 Rev Does Not Influence Viral Replication of Clade BC but Severely Reduces Viral Fitness of Clade B.Virologica Sinica · 2020Article
- Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China.Virology journal · 2019Article
- HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist.Oxidative medicine and cellular longevity · 2019Article
- Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014.Journal of the International AIDS Society · 2017Article
- Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses.Retrovirology · 2016Article
- Article
- Primer ID Informs Next-Generation Sequencing Platforms and Reveals Preexisting Drug Resistance Mutations in the HIV-1 Reverse Transcriptase Coding Domain.AIDS research and human retroviruses · 2015Article
- Reverse Transcription of Retroviruses and LTR Retrotransposons.Microbiology spectrum · 2015Review
- Altered viral fitness and drug susceptibility in HIV-1 carrying mutations that confer resistance to nonnucleoside reverse transcriptase and integrase strand transfer inhibitors.Journal of virology · 2014Article
- Article
- In vitro characterization of MK-1439, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor.Antimicrobial agents and chemotherapy · 2014Article
- The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy.AIDS research and therapy · 2014Article
- Reverse transcriptase backbone can alter the polymerization and RNase activities of non-nucleoside reverse transcriptase mutants K101E+G190S.The Journal of general virology · 2013Article
- Mutations in HIV-1 reverse transcriptase cause misfolding and miscleavage by the viral protease.Virology · 2013Article
- Efavirenz stimulates HIV-1 reverse transcriptase RNase H activity by a mechanism involving increased substrate binding and secondary cleavage activity.Biochemistry · 2013Article
- L74V increases the reverse transcriptase content of HIV-1 virions with non-nucleoside reverse transcriptase drug-resistant mutations L100I+K103N and K101E+G190S, which results in increased fitness.The Journal of general virology · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are important components of multidrug therapy for HIV-1. Understanding the effect of NNRTI-resistant mutants on virus replication and reverse transcriptase (RT) function is valuable for the development of extended-spectrum NNRTIs. We measured the fitness of six NNRTI-resistant mutants, the K103N, V106A, Y181C, G190A, G190S, and P236L viruses, using a flow cytometry-based cell culture assay. K103N and Y181C viruses had fitness similar to that of the wild type while V106A, G190A, G190S, and P236L viruses had reduced fitness. We also determined the biochemical correlates of fitness by measuring the RNase H and polymerization activities of recombinant mutant RTs and virion-associated RTs. The RNase H activities of recombinant and virion-associated RTs correlated with the relative fitness for each mutant. K103N and Y181C mutants had normal RNase H activity; V106A, G190A, and G190S mutants had moderate reductions in activity; and the P236L mutant had substantially reduced activity. With the exception of the P236L mutant, reduced fitness correlates with low virion-associated polymerization efficiency and reduced RT content. Reduced polymerase function in virions derived from low RT content rather than an intrinsic polymerization defect in each RT protein. In conclusion, severe defects in RNase H activity alone, exemplified by the P236L mutant, appear sufficient to cause a substantial reduction in fitness. For the other NNRTI mutants, reductions in RT content decreased both polymerization and RNase H activity in virions. RNase H reduction was compounded by intrinsic RNase H defects in the mutant RTs.
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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.