Novel mutation (V75T) in human immunodeficiency virus type 1 reverse transcriptase confers resistance to 2',3'-didehydro-2',3'-dideoxythymidine in cell culture

Antimicrob Agents Chemother. 1994 Jun;38(6):1428-32. doi: 10.1128/AAC.38.6.1428.


We have selected a human immunodeficiency virus type 1 (HIV-1) mutant strain with a moderate (sevenfold) level of resistance to the nucleoside analog 2',3'-didehydro-2',3'-dideoxythymidine (D4T or stavudine). After serial passage of the HXB2 strain of HIV-1 in MT4 cells, a novel mutation involving two nucleotide substitutions in codon 75 of the viral reverse transcriptase, altering valine to threonine, was seen. When introduced into a wild-type HIV-1 background by site-directed mutagenesis, the T-75 mutation conferred cross-resistance to the dideoxynucleosides dideoxyinosine and dideoxycytosine as well as to 2',3'-didehydro-2',3'-dideoxycytosine.

MeSH terms

  • Base Sequence
  • Cells, Cultured
  • Drug Resistance, Microbial
  • Emtricitabine / analogs & derivatives
  • HIV Reverse Transcriptase
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • RNA-Directed DNA Polymerase / genetics*
  • Reverse Transcriptase Inhibitors
  • Stavudine / pharmacology*
  • Zalcitabine / analogs & derivatives
  • Zalcitabine / pharmacology
  • Zidovudine / pharmacology


  • Reverse Transcriptase Inhibitors
  • Zidovudine
  • Zalcitabine
  • Stavudine
  • HIV Reverse Transcriptase
  • RNA-Directed DNA Polymerase
  • Emtricitabine
  • Racivir