ArticlePloS one2011
A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART.The Journal of antimicrobial chemotherapy · 2019Trial
- Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil.International journal of molecular sciences · 2021Article
- Anomalous Reverse Transcription through Chemical Modifications in Polyadenosine Stretches.Biochemistry · 2020Article
- A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort.BMC infectious diseases · 2019Article
- HIV-1 Subtype C with PYxE Insertion Has Enhanced Binding of Gag-p6 to Host Cell Protein ALIX and Increased Replication Fitness.Journal of virology · 2019Article
- An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs.The Journal of antimicrobial chemotherapy · 2017Article
- No Evidence That HIV-1 Subtype C Infection Compromises the Efficacy of Tenofovir-Containing Regimens: Cohort Study in the United Kingdom.The Journal of infectious diseases · 2016Article
- Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa.AIDS research and human retroviruses · 2016Article
- Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya.Journal of the International AIDS Society · 2016Article
- High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa.PloS one · 2015Article
- Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure.Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology · 2015Article
- Emerging antiretroviral drug resistance in sub-Saharan Africa: novel affordable technologies are needed to provide resistance testing for individual and public health benefits.AIDS (London, England) · 2014Article
- The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance.Viruses · 2014Review
- Impact of human immunodeficiency virus type-1 sequence diversity on antiretroviral therapy outcomes.Viruses · 2014Review
- Drug resistance in non-B subtype HIV-1: impact of HIV-1 reverse transcriptase inhibitors.Viruses · 2014Review
- Emergence of HIV drug resistance during first- and second-line antiretroviral therapy in resource-limited settings.The Journal of infectious diseases · 2013Review
- Identification and characterization of a novel HIV-1 nucleotide-competing reverse transcriptase inhibitor series.Antimicrobial agents and chemotherapy · 2013Article
- Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy.AIDS (London, England) · 2013Article
- Characterizing the emergence and persistence of drug resistant mutations in HIV-1 subtype C infections using 454 ultra deep pyrosequencing.BMC infectious diseases · 2013Article
- Low-abundance resistant mutations in HIV-1 subtype C antiretroviral therapy-naive individuals as revealed by pyrosequencing.Current HIV research · 2013Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Numerous studies have suggested that the K65R reverse transcriptase (RT) mutation develops more readily in subtype C than subtype B HIV-1. We recently showed that this discrepancy lies partly in the subtype C template coding sequence that predisposes RT to pause at the site of K65R mutagenesis. However, the mechanism underlying this observation and the elevated rates of K65R development remained unknown. Here, we report that DNA synthesis performed with subtype C templates consistently produced more K65R-containing transcripts than subtype B templates, regardless of the subtype-origin of the RT enzymes employed. These findings confirm that the mechanism involved is template-specific and RT-independent. In addition, a pattern of DNA synthesis characteristic of site-specific primer/template slippage and dislocation was only observed with the subtype C sequence. Analysis of RNA secondary structure suggested that the latter was unlikely to impact on K65R development between subtypes and that Streisinger strand slippage during DNA synthesis at the homopolymeric nucleotide stretch of the subtype C K65 region might occur, resulting in misalignment of the primer and template. Consequently, slippage would lead to a deletion of the middle adenine of codon K65 and the production of a -1 frameshift mutation, which upon dislocation and realignment of the primer and template, would lead to development of the K65R mutation. These findings provide additional mechanistic evidence for the facilitated development of the K65R mutation in subtype C HIV-1.
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