"Resistance" to PSC-RANTES revisited: two mutations in human immunodeficiency virus type 1 HIV-1 SF162 or simian-human immunodeficiency virus SHIV SF162-p3 do not confer resistance

J Virol. 2010 Jun;84(11):5842-5. doi: 10.1128/JVI.01907-09. Epub 2010 Mar 24.


Resistance of human immunodeficiency virus type 1 (HIV-1) to small-molecule CCR5 inhibitors is well demonstrated, but resistance to macromolecular CCR5 inhibitors (e.g., PSC-RANTES) that act by both CCR5 internalization and receptor blockade had not been reported until recently (3). The report of a single simian-human immunodeficiency virus SHIV(SF162-p3) variant with one V3 and one gp41 sequence change in gp160 that conferred both altered replicative fitness and resistance to PSC-RANTES was therefore surprising. We introduced the same two mutations into both the parental HIV-1(SF162) and the macaque-adapted SHIV(SF162-p3) and found minor differences in entry fitness but no changes in sensitivity to inhibition by either PSC-RANTES or the small-molecule allosteric inhibitor TAK-779. We attribute the earlier finding to confounding fitness effects with inhibitor sensitivity.

Publication types

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

MeSH terms

  • Animals
  • Anti-HIV Agents / pharmacology
  • CCR5 Receptor Antagonists
  • Chemokine CCL5 / pharmacology*
  • Drug Resistance / genetics*
  • HIV-1 / genetics*
  • HIV-1 / pathogenicity
  • Humans
  • Macaca
  • Mutation*
  • Receptors, Virus / antagonists & inhibitors
  • Simian Immunodeficiency Virus / genetics*
  • Simian Immunodeficiency Virus / pathogenicity
  • Virus Replication / drug effects


  • Anti-HIV Agents
  • CCR5 Receptor Antagonists
  • Chemokine CCL5
  • RANTES, N(alpha)-(n-nonanoyl)-desSer(1)-(thioproline(2),cyclohexylglycine(3))-
  • Receptors, Virus