ArticleAntimicrobial agents and chemotherapy2005
The L74V mutation in human immunodeficiency virus type 1 reverse transcriptase counteracts enhanced excision of zidovudine monophosphate associated with thymidine analog resistance mutations.
Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 66 citations in OpenAlex.
- Molecular Docking Studies of HIV-1 Resistance to Reverse Transcriptase Inhibitors: Mini-Review.Molecules (Basel, Switzerland) · 2018Review
- HIV Resistance Prediction to Reverse Transcriptase Inhibitors: Focus on Open Data.Molecules (Basel, Switzerland) · 2018Review
- High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy.The Pediatric infectious disease journal · 2017Article
- Resistance to reverse transcriptase inhibitors used in the treatment and prevention of HIV-1 infection.Future microbiology · 2015Review
- Molecular mechanism of HIV-1 resistance to 3'-azido-2',3'-dideoxyguanosine.Antiviral research · 2014Article
- HIV-1 reverse transcriptase and antiviral drug resistance. Part 2.Current opinion in virology · 2013Review
- Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance.Virology · 2013Article
- 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
- 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
- Mechanism of resistance to GS-9148 conferred by the Q151L mutation in HIV-1 reverse transcriptase.Antimicrobial agents and chemotherapy · 2011Article
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- N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations.AIDS (London, England) · 2010Article
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- Thymidine analogue resistance suppression by V75I of HIV-1 reverse transcriptase: effects of substituting valine 75 on stavudine excision and discrimination.The Journal of biological chemistry · 2009Article
- The human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor resistance mutation I132M confers hypersensitivity to nucleoside analogs.Journal of virology · 2009Article
- Structure and function of HIV-1 reverse transcriptase: molecular mechanisms of polymerization and inhibition.Journal of molecular biology · 2009Review
- Impact of human immunodeficiency virus type 1 reverse transcriptase inhibitor drug resistance mutation interactions on phenotypic susceptibility.AIDS research and human retroviruses · 2008Article
- Mechanisms by which the G333D mutation in human immunodeficiency virus type 1 Reverse transcriptase facilitates dual resistance to zidovudine and lamivudine.Antimicrobial agents and chemotherapy · 2008Article
- Variations in reverse transcriptase and RNase H domain mutations in human immunodeficiency virus type 1 clinical isolates are associated with divergent phenotypic resistance to zidovudine.Antimicrobial agents and chemotherapy · 2007Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Thymidine analog mutations (TAMs) in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) confer resistance to zidovudine (AZT) by increasing the rate of ATP-dependent phosphorolysis of the terminal nucleotide monophosphate (primer unblocking). By contrast, the L74V mutation, which confers resistance to didanosine, sensitizes HIV-1 to AZT and partially restores AZT susceptibility when present together with one or more TAMs. To compare rates of primer unblocking in RTs carrying different clusters of TAMs and to explore the biochemical mechanism by which L74V affects AZT susceptibility, ATP-mediated rescue of AZT-blocked DNA synthesis was assayed using a series of purified recombinant RTs. Rates of primer unblocking were higher in the 67N/70R/219Q RT than in the 41L/210W/215Y enzyme and were similar to rates observed with an RT carrying six TAMs (41L/67N/70R/210W/215Y/219Q). The presence of 74V in an otherwise wild-type RT reduced the rate of primer unblocking to a degree similar to that observed with the M184V mutation for lamivudine resistance, which also sensitizes HIV-1 to AZT. Introduction of 74V into RTs carrying TAMs partially counteracted the effect of TAMs on the rate of primer unblocking. The effect of 74V was less marked than that of the 184V mutation in the 67N/70R/219Q and 41L/210W/215Y RTs but similar in the RT carrying six TAMs. These results demonstrate that L74V enhances AZT susceptibility by reducing the extent of its removal by ATP-dependent phosphorolysis and provides further evidence for a common mechanism by which mutations conferring resistance to didanosine and lamivudine sensitize HIV-1 to AZT.
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