ArticleAntimicrobial agents and chemotherapy2004
Molecular mechanisms of tenofovir resistance conferred by human immunodeficiency virus type 1 reverse transcriptase containing a diserine insertion after residue 69 and multiple thymidine analog-associated mutations.
Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 70 citations in OpenAlex.
- Insights into HIV-1 Reverse Transcriptase (RT) Inhibition and Drug Resistance from Thirty Years of Structural Studies.Viruses · 2022Review
- A Combination of Amino Acid Mutations Leads to Resistance to Multiple Nucleoside Analogs in Reverse Transcriptases from HIV-1 Subtypes B and C.Antimicrobial agents and chemotherapy · 2022Article
- Avoiding Drug Resistance in HIV Reverse Transcriptase.Chemical reviews · 2021Review
- Cardiac complications in inherited mitochondrial diseases.Heart failure reviews · 2021Review
- Nucleocapsid Protein Precursors NCp9 and NCp15 Suppress ATP-Mediated Rescue of AZT-Terminated Primers by HIV-1 Reverse Transcriptase.Antimicrobial agents and chemotherapy · 2020Article
- Bioinformatic data processing pipelines in support of next-generation sequencing-based HIV drug resistance testing: the Winnipeg Consensus.Journal of the International AIDS Society · 2018Article
- Amino acid residues in HIV-2 reverse transcriptase that restrict the development of nucleoside analogue resistance through the excision pathway.The Journal of biological chemistry · 2018Article
- Structural Insights into HIV Reverse Transcriptase Mutations Q151M and Q151M Complex That Confer Multinucleoside Drug Resistance.Antimicrobial agents and chemotherapy · 2017Article
- Modeling the functional state of the reverse transcriptase of hepatitis B virus and its application to probing drug-protein interaction.BMC bioinformatics · 2016Article
- Subtype-specific analysis of the K65R substitution in HIV-1 that confers hypersusceptibility to a novel nucleotide-competing reverse transcriptase inhibitor.Antimicrobial agents and chemotherapy · 2015Article
- HIV-1 reverse transcriptase and antiviral drug resistance. Part 2.Current opinion in virology · 2013Review
- Article
- Understanding the molecular mechanism of sequence dependent tenofovir removal by HIV-1 reverse transcriptase: differences in primer binding site versus polypurine tract.Antiviral research · 2012Article
- In vitro resistance profile of the candidate HIV-1 microbicide drug dapivirine.Antimicrobial agents and chemotherapy · 2012Article
- Altered strand transfer activity of a multiple-drug-resistant human immunodeficiency virus type 1 reverse transcriptase mutant with a dipeptide fingers domain insertion.Journal of molecular biology · 2012Article
- Molecular dynamics simulation in virus research.Frontiers in microbiology · 2012Article
- Mechanism of resistance to GS-9148 conferred by the Q151L mutation in HIV-1 reverse transcriptase.Antimicrobial agents and chemotherapy · 2011Article
- Structural basis of HIV-1 resistance to AZT by excision.Nature structural & molecular biology · 2010Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Two amino acids inserted between residues 69 and 70 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) are rare mutations that may develop in viruses containing multiple thymidine analog (zidovudine [AZT], stavudine)-associated mutations and that confer high-level resistance to all currently approved chain-terminating nucleoside and nucleotide RT inhibitors (NRTIs). The two known mechanisms of resistance to NRTIs are decreased incorporation and increased excision. The mechanism used by RT insertion mutants has not been described for tenofovir (TFV), a recently approved agent in this class. A patient-derived HIV-1 strain (strain FS-SSS) that contained an insertion mutation in a background of additional resistance mutations M41L, L74V, L210W, and T215Y was obtained. A second virus (strain FS) was derived from FS-SSS. In strain FS the insertion and T69S were reverted but the other resistance mutations were retained. The FS virus showed strong resistance to AZT but low-level changes in susceptibilities to other NRTIs and TFV. The FS-SSS virus showed reduced susceptibilities to all NRTIs including TFV. Steady-state kinetics demonstrated that the relative binding or incorporation of TFV was slightly decreased for FS-SSS RT compared to those for wild-type RT. However, significant ATP-mediated excision of TFV was detected for both mutant RT enzymes and followed the order FS-SSS RT > FS RT > wild-type RT. The presence of physiological concentrations of the +1 nucleotide inhibited TFV excision by the wild-type RT and slightly inhibited excision by the FS RT, whereas the level of excision by the FS-SSS RT remained high. Computer modeling suggests that the increased mobility of the beta3-beta4 loop may contribute to the high-level and broad NRTI resistance caused by the T69 insertion mutation.
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