Sensitivity/resistance profile of a simian immunodeficiency virus containing the reverse transcriptase gene of human immunodeficiency virus type 1 (HIV-1) toward the HIV-1-specific non-nucleoside reverse transcriptase inhibitors

Biochem Biophys Res Commun. 1995 Jun 26;211(3):850-6. doi: 10.1006/bbrc.1995.1890.

Abstract

To develop an animal model for the therapy of AIDS with human immunodeficiency virus type 1 (HIV-1)-specific reverse transcriptase (RT) inhibitors, we recently constructed a hybrid simian immunodeficiency virus (SIV)/HIV-1 in which the RT gene of SIV was replaced by the RT gene of HIV-1. This chimaeric virus, designated RT-SHIV, was found to be markedly sensitive to the inhibitory effects of both nucleoside (ddN) and non-nucleoside RT inhibitors (NNRTIs). In contrast, SIV was inhibited only by ddNs (i.e., 3TC and AZT), but not NNRTIs. When RT-SHIV was grown in the presence of 3TC, nevirapine, TSAO-m3T or the thiocarboxanilide UC-42 drug-resistant mutant virus strains emerged in cell culture as rapid as for HIV-1(IIIB). The antiviral sensitivity/resistance spectrum of the mutant RT-SHIV strains against NNRTIs and ddNs, and the nature of the mutations that appeared in their RT were similar to those of the mutant HIV-1 strains that were selected under identical experimental conditions. Infection of macaques with RT-SHIV may be a useful tool for studying the mechanism of NNRTI-resistance development and the therapy of NNRTI-resistant viruses in an animal model.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy
  • Antiviral Agents / pharmacology*
  • Base Sequence
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical / methods*
  • Drug Resistance, Microbial
  • HIV Reverse Transcriptase
  • HIV-1 / enzymology
  • HIV-1 / genetics*
  • Microbial Sensitivity Tests / methods*
  • Molecular Sequence Data
  • Mutation
  • RNA-Directed DNA Polymerase / genetics
  • Recombinant Proteins / drug effects
  • Reverse Transcriptase Inhibitors*
  • Simian Immunodeficiency Virus / drug effects
  • Simian Immunodeficiency Virus / genetics

Substances

  • Antiviral Agents
  • Recombinant Proteins
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • RNA-Directed DNA Polymerase