Production of specific mRNA transcripts, usage of an alternate promoter, and octamer-binding transcription factors influence the surface expression levels of the HIV coreceptor CCR5 on primary T cells

J Immunol. 2007 May 1;178(9):5668-81. doi: 10.4049/jimmunol.178.9.5668.


Surface levels of CCR5 on memory CD4(+) T cells influence HIV-1/AIDS susceptibility. Alternative promoter usage results in the generation of CCR5 mRNA isoforms that differ based on whether they contain or lack the untranslated exon 1. The impact of exon 1-containing transcripts on CCR5 surface expression is unknown. In this study, we show that the increased cell surface expression of CCR5 on primary T cells is associated with selective enrichment of exon 1-containing transcripts. The promoter that drives exon 1-containing transcripts is highly active in primary human T cells but not in transformed T cell lines. The transcription factors Oct-1 and -2 inhibit and enhance, respectively, the expression of exon 1-containing transcripts and CCR5 surface levels. However, polymorphisms at homologous octamer-binding sites in the CCR5 promoter of nonhuman primates abrogate the binding of these transcription factors. These results identify exon 1-containing transcripts, and the cis-trans factors that regulate the expression levels of these mRNA isoforms as key parameters that affect CCR5 surface expression levels, and by extension, susceptibility to HIV/AIDS among humans, and possibly, the observed interspecies differences in susceptibility to lentiviral infection.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Exons
  • Gene Expression Regulation*
  • HIV-1 / immunology*
  • Humans
  • Molecular Sequence Data
  • Octamer Transcription Factor-1 / genetics
  • Octamer Transcription Factor-1 / metabolism*
  • Octamer Transcription Factor-2 / genetics
  • Octamer Transcription Factor-2 / metabolism*
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / metabolism
  • Receptors, CCR5 / analysis
  • Receptors, CCR5 / genetics*
  • Receptors, CCR5 / metabolism
  • Transcription, Genetic


  • Octamer Transcription Factor-1
  • Octamer Transcription Factor-2
  • RNA, Messenger
  • Receptors, CCR5