ArticleAntimicrobial agents and chemotherapy2008
Mechanisms by which the G333D mutation in human immunodeficiency virus type 1 Reverse transcriptase facilitates dual resistance to zidovudine and lamivudine.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 40 citations in OpenAlex.
- Mutation V111I in HIV-2 reverse transcriptase increases the fitness of the nucleoside analogue-resistant K65R and Q151M viruses.Journal of virology · 2015Article
- Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity.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
- Article
- A role of template cleavage in reduced excision of chain-terminating nucleotides by human immunodeficiency virus type 1 reverse transcriptase containing the M184V mutation.Journal of virology · 2012Article
- HIV-1 Reverse Transcriptase Still Remains a New Drug Target: Structure, Function, Classical Inhibitors, and New Inhibitors with Innovative Mechanisms of Actions.Molecular biology international · 2012Article
- The effects of RNase H inhibitors and nevirapine on the susceptibility of HIV-1 to AZT and 3TC.Virology · 2011Article
- The base component of 3'-azido-2',3'-dideoxynucleosides influences resistance mutations selected in HIV-1 reverse transcriptase.Antimicrobial agents and chemotherapy · 2011Article
- Phenotypic characterization of drug resistance-associated mutations in HIV-1 RT connection and RNase H domains and their correlation with thymidine analogue mutations.The Journal of antimicrobial chemotherapy · 2011Article
- Mechanisms involved in the selection of HIV-1 reverse transcriptase thumb subdomain polymorphisms associated with nucleoside analogue therapy failure.Antimicrobial agents and chemotherapy · 2010Article
- N348I in HIV-1 reverse transcriptase can counteract the nevirapine-mediated bias toward RNase H cleavage during plus-strand initiation.The Journal of biological chemistry · 2010Article
- Article
- A novel molecular mechanism of dual resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors.Journal of virology · 2010Article
- Subtype-specific differences in the human immunodeficiency virus type 1 reverse transcriptase connection subdomain of CRF01_AE are associated with higher levels of resistance to 3'-azido-3'-deoxythymidine.Journal of virology · 2009Article
- Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naïve patients.Antiviral research · 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
- Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms.The Journal of biological chemistry · 2008Article
- HIV-1 reverse transcriptase connection subdomain mutations reduce template RNA degradation and enhance AZT excision.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
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5 authors at 1 institution in 1 country.
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Abstract
Recent studies have identified a role for mutations in the connection and RNase H domains of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) resistance to nucleoside analog RT inhibitors (NRTI). To provide insight into the biochemical mechanism(s) involved, we investigated the effect of the G333D mutation in the connection domain of RT on resistance to zidovudine (AZT) and lamivudine (3TC) in enzymes that contain both M184V and thymidine analog mutations (TAMs; M41L, L210W, and T215Y). Our results from steady-state kinetic, pre-steady-state kinetic, and thermodynamic analyses indicate that G333D facilitates dual resistance to AZT and 3TC in two ways. First, in combination with M184V, G333D increased the ability of HIV-1 RT to effectively discriminate between the normal substrate dCTP and 3TC-triphosphate. Second, G333D enhanced the ability of RT containing TAMs and M184V to bind template/primer terminated by AZT-monophosphate (AZT-MP), thereby restoring ATP-mediated excision of AZT-MP under steady-state assay conditions. This study is the first to elucidate a molecular mechanism whereby a mutation in the connection domain of RT can affect NRTI susceptibility at the enzyme level.
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