Mutations at codon 184 in simian immunodeficiency virus reverse transcriptase confer resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine.
Variants of simian immunodeficiency virus (SIV) that display greater than 2,000-fold resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine (3TC) were generated through in vitro passage and drug selection. The polymerase regions of several of these resistant viruses were sequenced and were found to share either of two codon alterations at site 184 in reverse transcriptase (ATG to ATA [methionine to isoleucine] and ATG to GTA [methionine to valine]). The biological relevance of these substitutions for 3TC was confirmed by site-directed mutagenesis with the SIVmac239 infectious recombinant clone of SIV.
Cherry
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E
McGill University AIDS Centre, Jewish General Hospital, Montreal, Quebec, Canada.
Slater
M
M
Salomon
H
H
Rud
E
E
Wainberg
M A
MA
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D003001:Cloning, Molecular; D003062:Codon; D004352:Drug Resistance, Microbial / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D015302:Simian Immunodeficiency Virus / Q000201:enzymology* / Q000235:genetics*; D013237:Stereoisomerism; D013601:T-Lymphocytes / Q000821:virology; D014764:Viral Proteins / Q000235:genetics*; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D003062:Codon; D018894:Reverse Transcriptase Inhibitors; D014764:Viral Proteins; D019259:Lamivudine; D012194:RNA-Directed DNA Polymerase