Differential sensitivities of retroviruses to integrase strand transfer inhibitors

J Virol. 2011 Apr;85(7):3677-82. doi: 10.1128/JVI.02541-10. Epub 2011 Jan 26.

Abstract

Integrase inhibitors are emerging anti-human immunodeficiency virus (HIV) drugs, and multiple retroviruses and transposable elements were evaluated here for susceptibilities to raltegravir (RAL) and elvitegravir (EVG). All viruses, including primate and nonprimate lentiviruses, a Betaretrovirus, a Gammaretrovirus, and the Alpharetrovirus Rous sarcoma virus (RSV), were susceptible to inhibition by RAL. EVG potently inhibited all lentiviruses and intermediately inhibited Betaretrovirus and Gammaretrovirus infections yet was basically ineffective against RSV. Substitutions based on HIV type 1 (HIV-1) resistance changes revealed that integrase residue Ser150 contributed significantly to the resistance of RSV. The drugs intermediately inhibited intracisternal A-particle retrotransposition but were inactive against Sleeping Beauty transposition and long interspersed nucleotide element 1 (LINE-1) retrotransposition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Drug Resistance, Viral
  • Humans
  • Integrases / metabolism*
  • Primates
  • Pyrrolidinones / pharmacology
  • Quinolones / pharmacology
  • Raltegravir Potassium
  • Retroelements / drug effects
  • Retroviridae / drug effects*
  • Retroviridae / enzymology*
  • Virus Integration / drug effects*

Substances

  • Antiviral Agents
  • JTK 303
  • Pyrrolidinones
  • Quinolones
  • Retroelements
  • Raltegravir Potassium
  • Integrases