ArticleAntimicrobial agents and chemotherapy1997
Limiting deoxynucleoside triphosphate concentrations emphasize the processivity defect of lamivudine-resistant variants of human immunodeficiency virus type 1 reverse transcriptase.
Article in Antimicrobial agents and chemotherapy, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Effects of the W153L substitution in HIV reverse transcriptase on viral replication and drug resistance to multiple categories of reverse transcriptase inhibitors.Antimicrobial agents and chemotherapy · 2014Article
- The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity.Journal of virology · 2014Article
- Interrelationship between HIV-1 fitness and mutation rate.Journal of molecular biology · 2013Article
- Subunit-selective mutational analysis and tissue culture evaluations of the interactions of the E138K and M184I mutations in HIV-1 reverse transcriptase.Journal of virology · 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
- A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus.Virology journal · 2011Article
- Mutations in the thumb allow human immunodeficiency virus type 1 reverse transcriptase to be cleaved by protease in virions.Journal of virology · 2009Article
- Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V.Antiviral research · 2009Article
- HIV-1 Transmission, Replication Fitness and Disease Progression.Virology : research and treatment · 2008Article
- Apparent defects in processive DNA synthesis, strand transfer, and primer elongation of Met-184 mutants of HIV-1 reverse transcriptase derive solely from a dNTP utilization defect.The Journal of biological chemistry · 2008Article
- Reduced dNTP binding affinity of 3TC-resistant M184I HIV-1 reverse transcriptase variants responsible for viral infection failure in macrophage.The Journal of biological chemistry · 2008Article
- Human immunodeficiency virus type 1: resistance to nucleoside analogues and replicative capacity in primary human macrophages.Journal of virology · 2007Article
- Effect of cell cycle arrest on the activity of nucleoside analogues against human immunodeficiency virus type 1.Journal of virology · 2005Article
- Quantification of the effects on viral DNA synthesis of reverse transcriptase mutations conferring human immunodeficiency virus type 1 resistance to nucleoside analogues.Journal of virology · 2005Article
- Role of minority populations of human immunodeficiency virus type 1 in the evolution of viral resistance to protease inhibitors.Journal of virology · 2004Article
- Infectivity and replication capacity of drug-resistant human immunodeficiency virus type 1 variants isolated during primary infection.Journal of virology · 2003Article
- Extended spectrum of HIV-1 reverse transcriptase mutations in patients receiving multiple nucleoside analog inhibitors.AIDS (London, England) · 2003Article
- The M184V mutation in reverse transcriptase can delay reversion of attenuated variants of simian immunodeficiency virus.Journal of virology · 2002Article
- Genotypic testing for human immunodeficiency virus type 1 drug resistance.Clinical microbiology reviews · 2002Review
- Kinetic analysis of wild-type and YMDD mutant hepatitis B virus polymerases and effects of deoxyribonucleotide concentrations on polymerase activity.Antimicrobial agents and chemotherapy · 2002Article
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Abstract
The nucleoside drug lamivudine (3TC) triggers the selection of resistant forms of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) with a substitution of amino acid 184Met. The 3TC-resistant RT enzymes 184Val and 184Ile exhibit a processivity defect in in vitro assays that correlates with reduced replication of the corresponding virus variants in primary cells. However, no replication defect is apparent for these two mutants in the transformed T-cell line SupT1. One obvious difference between the two cell types is the intracellular deoxynucleoside triphosphate (dNTP) level. Primary cells have a much smaller dNTP pool, and this cellular condition may emphasize the processivity defect of the codon 184 RT variants. Alternatively, cell-specific cofactors that influence the process of reverse transcription may exist. Such accessory factors may be packaged into the virion to exert an effect on the RT enzyme. To discriminate between these possibilities we performed additional assays with the wild-type and mutant RT enzymes. The RT proteins were either isolated from virions produced by primary and transformed cell types or expressed as recombinant protein. We also performed infection assays with cells treated with a drug that reduces the intracellular dNTP pool. Furthermore, reverse transcription was studied within virus particles in the endogenous assay, which allows for the manipulation of the dNTP level. The combined results indicate that the enzymatic defect of the 3TC-resistant HIV-1 variants is stressed at low dNTP concentrations.
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