The same mutation that encodes low-level human immunodeficiency virus type 1 resistance to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine confers high-level resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine

Antimicrob Agents Chemother. 1993 Jun;37(6):1390-2. doi: 10.1128/aac.37.6.1390.

Abstract

Variants of human immunodeficiency virus type 1 that display 500- to 1,000-fold resistance to the (-) enantiomer of 2'-deoxy-3'-thiacytidine and approximately 4- to 8-fold resistance to 2',3'-dideoxycytidine and 2',3'-dideoxyinosine have been generated through in vitro selection with the former compound. The polymerase regions of several of these resistant viruses shared a codon alteration at site 184 (ATG-->GTG; methionine-->valine), a mutation previously associated with low-level resistance to 2',3'-dideoxycytidine. The biological relevance of this mutation for the (-) enantiomer of 2'-deoxy-3'-thiacytidine was confirmed by site-directed mutagenesis with the HXB2-D clone of human immunodeficiency virus type 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Base Sequence
  • Cloning, Molecular
  • Didanosine / pharmacology*
  • Drug Resistance, Microbial
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • Humans
  • Lamivudine
  • Methionine / genetics
  • Mutagenesis, Site-Directed / genetics
  • Mutation
  • Stereoisomerism
  • Valine / genetics
  • Zalcitabine / analogs & derivatives*
  • Zalcitabine / pharmacology*

Substances

  • Antiviral Agents
  • Lamivudine
  • Zalcitabine
  • Methionine
  • Valine
  • Didanosine