High-level resistance to (-) enantiomeric 2'-deoxy-3'-thiacytidine in vitro is due to one amino acid substitution in the catalytic site of human immunodeficiency virus type 1 reverse transcriptase

Antimicrob Agents Chemother. 1993 Oct;37(10):2231-4. doi: 10.1128/AAC.37.10.2231.


Passage of human immunodeficiency virus type 1 in the presence of increasing 2'-deoxy-3'-thiacytidine (3TC) concentrations results in high-level (> 100-fold) 3TC-resistant viruses. All 3TC-resistant viruses possess a substitution at the second codon (from a methionine into an isoleucine) at position 184 within the highly conserved motif (YMDD) of human immunodeficiency virus type 1 reverse transcriptase. 3TC-resistant viruses were cross-resistant to the (-) enantiomer of the fluorinated derivative of BCH-189 but remained susceptible to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine. The susceptibilities of the 3TC-resistant viruses to the (+) enantiomers of BCH-189 and the fluorinated derivative of BCH-189 demonstrate an enantiomeric specificity for viruses selected under these conditions. Introduction of an isoleucine substitution at codon 184 into a background of two known 3'-azido-3'-deoxythymidine resistance mutations (amino acids 41 and 215) restored the susceptibility of this virus to 3'-azido-3'-deoxythymidine.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Base Sequence
  • Binding Sites
  • Codon / genetics
  • Drug Resistance, Microbial
  • HIV Reverse Transcriptase
  • HIV-1 / enzymology*
  • HIV-1 / genetics*
  • Humans
  • Isoleucine / genetics
  • Lamivudine
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Mutation / genetics
  • RNA-Directed DNA Polymerase / genetics*
  • Reverse Transcriptase Inhibitors
  • Stereoisomerism
  • Zalcitabine / analogs & derivatives*
  • Zalcitabine / pharmacology


  • Antiviral Agents
  • Codon
  • Reverse Transcriptase Inhibitors
  • Isoleucine
  • Lamivudine
  • Zalcitabine
  • HIV Reverse Transcriptase
  • RNA-Directed DNA Polymerase