rdf:type |
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lifeskim:mentions |
|
pubmed:issue |
16
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pubmed:dateCreated |
1997-9-17
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pubmed:abstractText |
Human immunodeficiency virus type 1 (HIV-1) variants with resistance mutations in the reverse transcriptase (RT) gene appear during drug therapy with the nucleoside analogue 2',3'-dideoxy-3'-thiacytidine (3TC). These 3TC-resistant RT variants have a single point mutation that changes the 184Met residue into either Val or Ile. Both codon 184 variants are frequently observed in 3TC-treated patients and can also be selected in cell culture infections. We demonstrated previously that the 184Ile and 184Val RT enzymes exhibit a processivity defect in in vitro assays, with 184Ile being the least processive enzyme [Met(wt) >Val >Ile]. In this study, we measured the polymerase fidelity of the wild-type (184Met) and 3TC-resistant RT enzymes (184Ile and 184Val) on DNA and RNA templates. Both virion- extracted and Escherichia coli -expressed recombinant RT enzymes were used to measure the nucleotide misinsertion and mispair extension efficiencies. The 3TC-resistant enzymes were more accurate than the wild-type RT protein in both type of assays. The order of accuracy observed for the codon 184 variants [Ile >Val >Met(wt)] may suggest an inverse correlation between the fidelity and processivity properties of these enzymes.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9241233-1052321,
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
|
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0305-1048
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3212-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:9241233-DNA,
pubmed-meshheading:9241233-Drug Resistance,
pubmed-meshheading:9241233-HIV Reverse Transcriptase,
pubmed-meshheading:9241233-Lamivudine,
pubmed-meshheading:9241233-Point Mutation,
pubmed-meshheading:9241233-RNA,
pubmed-meshheading:9241233-Recombinant Proteins,
pubmed-meshheading:9241233-Structure-Activity Relationship,
pubmed-meshheading:9241233-Substrate Specificity,
pubmed-meshheading:9241233-Templates, Genetic
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pubmed:year |
1997
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pubmed:articleTitle |
Increased polymerase fidelity of the 3TC-resistant variants of HIV-1 reverse transcriptase.
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pubmed:affiliation |
Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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