Inefficient entry of vicriviroc-resistant HIV-1 via the inhibitor-CCR5 complex at low cell surface CCR5 densities Academic Article uri icon


MeSH Major

  • CCR5 Receptor Antagonists
  • HIV Infections
  • HIV-1
  • Piperazines
  • Pyrimidines
  • Receptors, CCR5


  • HIV-1 variants resistant to small molecule CCR5 inhibitors such as vicriviroc (VVC) have modified Env complexes that can use both the inhibitor-bound and -free forms of the CCR5 co-receptor to enter target cells. However, entry via the inhibitor-CCR5 complex is inefficient in some, but not all, cell types, particularly cell lines engineered to express CCR5. We investigated the effect of increasing CCR5 expression, and hence the density of the inhibitor-CCR5 complex when a saturating inhibitor (VVC) concentration was present, by using 293-Affinofile cells, in which CCR5 expression is up-regulated by the transcriptional activator, ponasterone. When CCR5 expression was low, the resistant virus entered the target cells to a lesser extent when VVC was present than absent. However, at a higher CCR5 level, there was much less entry inhibition at a constant, saturating VVC concentration. We conclude that the relative decrease in entry of a VVC-resistant virus in some cell types results from its less efficient use of the VVC-CCR5 complex, and that increasing the CCR5 expression level can compensate for this inefficiency.

publication date

  • May 10, 2009



  • Academic Article



  • eng

PubMed Central ID

  • PMC2674391

Digital Object Identifier (DOI)

  • 10.1016/j.virol.2009.02.044

PubMed ID

  • 19303620

Additional Document Info

start page

  • 296

end page

  • 302


  • 387


  • 2