Nevirapine resistance mutation at codon 181 of the HIV-1 reverse transcriptase confers stavudine resistance by increasing nucleotide substrate discrimination and phosphorolytic activity

J Biol Chem. 2003 May 2;278(18):15469-72. doi: 10.1074/jbc.C300022200. Epub 2003 Feb 24.

Abstract

Recombinant HIV-1 reverse transcriptase (RT) carrying non-nucleoside inhibitors (NNRTIs) resistance mutation at codon 181 showed reduced incorporation and high efficiency of phosphorolytic removal of stavudine, a nucleoside RT inhibitor. These results reveal a new mechanism for cross-resistance between different classes of HIV-1 RT inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Codon*
  • Drug Resistance, Viral*
  • HIV Reverse Transcriptase / genetics*
  • Mutation*
  • Nevirapine / pharmacology*
  • Nucleotides / metabolism
  • Phosphorylation
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Stavudine / pharmacology*
  • Zidovudine / pharmacology

Substances

  • Codon
  • Nucleotides
  • Reverse Transcriptase Inhibitors
  • Zidovudine
  • Nevirapine
  • Stavudine
  • HIV Reverse Transcriptase