HIV-1-specific reverse transcriptase inhibitors show differential activity against HIV-1 mutant strains containing different amino acid substitutions in the reverse transcriptase

Virology. 1993 Jan;192(1):246-53. doi: 10.1006/viro.1993.1027.


Serial passage of HIV-1 in CEM or MT-4 cell cultures in the presence of different HIV-1-specific reverse transcriptase (RT) inhibitors yielded mutant viruses which were resistant (i.e., 200- to 1000-fold less sensitive) to the homologous compounds. The RT of these mutant HIV-1 strains showed different amino acid substitutions depending on the class of the HIV-1-specific RT inhibitors. The following amino acid substitutions were found: 138 Glu-->Lys (TSAO-T), 181 Tyr-->Cys (nevirapine), 181 Tyr-->Cys (pyridinone), and 100 Leu-->Ile (TIBO R82150). Four TIBO (R82913)-resistant HIV-1 strains contained different amino acid substitutions: 103 Lys-->Asn (strain 2), 100 Leu-->Ile and 138 Glu-->Lys (strain B02), 100 Leu-->Ile and 181 Tyr-->Cys (strain 1), 100 Leu-->Ile and 188 Tyr-->His (strain B22). The level of cross-resistance (or sensitivity) highly depends on the nature of the amino acid substitutions. As a rule, the TSAO-resistant HIV-1 strains (138 Glu-->Lys) and TIBO (R82150 or R82913)-resistant HIV-1 strains (Leu 100-->Ile or 103 Lys-->Asn) are sensitive to the other HIV-1-specific RT inhibitors, whereas the amino acid change 181 Tyr-->Cys results in a significant reduction of sensitivity to all classes of the HIV-1-specific RT inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Genes, pol
  • HIV Reverse Transcriptase
  • HIV-1 / enzymology*
  • HIV-1 / growth & development
  • Molecular Sequence Data
  • Mutation
  • Oligodeoxyribonucleotides / chemistry
  • RNA-Directed DNA Polymerase / chemistry
  • RNA-Directed DNA Polymerase / genetics
  • Reverse Transcriptase Inhibitors*
  • Structure-Activity Relationship
  • Virus Replication


  • Oligodeoxyribonucleotides
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • RNA-Directed DNA Polymerase