ArticleThe Biochemical journal2007
Characterization of novel non-nucleoside reverse transcriptase (RT) inhibitor resistance mutations at residues 132 and 135 in the 51 kDa subunit of HIV-1 RT.
Article in The Biochemical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase.Frontiers in molecular biosciences · 2022Article
- From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Structural Maturation of HIV-1 Reverse Transcriptase-A Metamorphic Solution to Genomic Instability.Viruses · 2016Review
- Novel Mutations L228I and Y232H Cause Nonnucleoside Reverse Transcriptase Inhibitor Resistance in Combinational Pattern.AIDS research and human retroviruses · 2016Article
- Novel high-throughput screen identifies an HIV-1 reverse transcriptase inhibitor with a unique mechanism of action.The Biochemical journal · 2014Article
- Role of the K101E substitution in HIV-1 reverse transcriptase in resistance to rilpivirine and other nonnucleoside reverse transcriptase inhibitors.Antimicrobial agents and chemotherapy · 2013Article
- Effect of mutations at position E138 in HIV-1 reverse transcriptase and their interactions with the M184I mutation on defining patterns of resistance to nonnucleoside reverse transcriptase inhibitors rilpivirine and etravirine.Antimicrobial agents and chemotherapy · 2013Article
- Molecular mechanism of antagonism between the Y181C and E138K mutations in HIV-1 reverse transcriptase.Journal of virology · 2012Article
- F18, a novel small-molecule nonnucleoside reverse transcriptase inhibitor, inhibits HIV-1 replication using distinct binding motifs as demonstrated by resistance selection and docking analysis.Antimicrobial agents and chemotherapy · 2012Article
- Compensation by the E138K mutation in HIV-1 reverse transcriptase for deficits in viral replication capacity and enzyme processivity associated with the M184I/V mutations.Journal of virology · 2011Article
- Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase.Retrovirology · 2011Article
- Synthesis and Anti-HIV-1 Activity of a Novel Series of Aminoimidazole Analogs.Letters in drug design & discovery · 2010Article
- The human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor resistance mutation I132M confers hypersensitivity to nucleoside analogs.Journal of virology · 2009Article
- Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance.Biochemistry · 2008Article
- Mechanisms of inhibition of HIV replication by non-nucleoside reverse transcriptase inhibitors.Virus research · 2008Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Several rare and novel NNRTI [non-nucleoside reverse transcriptase (RT) inhibitor] resistance mutations were recently detected at codons 132 and 135 in RTs from clinical isolates using the yeast-based chimaeric TyHRT (Ty1/HIV-1 RT) phenotypic assay. Ile132 and Ile135 form part of the beta7-beta8 loop of HIV-1 RT (residues 132-140). To elucidate the contribution of these residues in RT structure-function and drug resistance, we constructed twelve recombinant enzymes harbouring mutations at codons 132 and 135-140. Several of the mutant enzymes exhibited reduced DNA polymerase activities. Using the yeast two-hybrid assay for HIV-1 RT dimerization we show that in some instances this decrease in enzyme activity could be attributed to the mutations, in the context of the 51 kDa subunit of HIV-1 RT, disrupting the subunit-subunit interactions of the enzyme. Drug resistance analyses using purified RT, the TyHRT assay and antiviral assays demonstrated that the I132M mutation conferred high-level resistance (>10-fold) to nevirapine and delavirdine and low-level resistance (approximately 2-3-fold) to efavirenz. The I135A and I135M mutations also conferred low level NNRTI resistance (approximately 2-fold). Subunit selective mutagenesis studies again demonstrated that resistance was conferred via the p51 subunit of HIV-1 RT. Taken together, our results highlight a specific role of residues 132 and 135 in NNRTI resistance and a general role for residues in the beta7-beta8 loop in the stability of HIV-1 RT.
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