TCR triggering transcriptionally downregulates CCR5 expression on rhesus macaque CD4(+) T-cells with no measurable effect on susceptibility to SIV infection

Virology. 2011 Jan 5;409(1):132-40. doi: 10.1016/j.virol.2010.10.005. Epub 2010 Oct 28.

Abstract

Studies using transformed human cell lines suggest that most SIV strains use CCR5 as co-receptor. Our analysis of primary rhesus macaque CD4(+) T-cell clones revealed marked differences in susceptibility to SIV(mac)239 infection. We investigated whether different levels of CCR5 expression account for clonal differences in SIV(mac)239 susceptibility. Macaque CD4(+) T-cells showed significant CCR5 downregulation 1-2days following CD3 mAb stimulation, which gradually recovered at resting state, 7-10days after activation. Exposure of clones to SIV(mac)239 during their CCR5(low) or CCR5(high) expression states revealed differences in SIV susceptibility independent of surface CCR5 levels. Furthermore, a CCR5 antagonist similarly reduced SIV(mac)239 infection of clones during their CCR5(low) or CCR5(high) expression states. Our data suggest a model where i) very low levels of CCR5 are sufficient for efficient SIV infection, ii) CCR5 levels above this threshold do not enhance infection, and iii) low level infection can occur in the absence of CCR5.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • CCR5 Receptor Antagonists
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / virology
  • Cell Line
  • DNA, Viral / analysis
  • Down-Regulation*
  • Female
  • Gene Products, gag / genetics
  • Gene Products, gag / immunology
  • Gene Products, gag / metabolism
  • Humans
  • Macaca mulatta
  • Male
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / metabolism*
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / pathogenicity*

Substances

  • Antibodies, Monoclonal
  • CCR5 Receptor Antagonists
  • CD3 Complex
  • DNA, Viral
  • Gag protein p27, Simian immunodeficiency virus
  • Gene Products, gag
  • Receptors, Antigen, T-Cell
  • Receptors, CCR5