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

Srinivas Mummidi, Lisa M. Adams, Scott E. VanCompernolle, Mrunal Kalkonde, Jose F. Camargo, Hemant Kulkarni, Adam S. Bellinger, Gregory Bonello, Hiromi Tagoh, Seema S. Ahuja, Derya Unutmaz, Sunil K. Ahuja

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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 nnRNA 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.

Original languageEnglish (US)
Pages (from-to)5668-5681
Number of pages14
JournalJournal of Immunology
Volume178
Issue number9
DOIs
StatePublished - May 1 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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