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

14 Citations (Scopus)

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
StatePublished - May 1 2007

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Octamer Transcription Factors
Exons
HIV
T-Lymphocytes
Messenger RNA
Octamer Transcription Factor-2
Octamer Transcription Factor-1
Acquired Immunodeficiency Syndrome
RNA Isoforms
Transformed Cell Line
Primates
HIV-1
Protein Isoforms
Transcription Factors
Binding Sites
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

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

In: Journal of Immunology, Vol. 178, No. 9, 01.05.2007, p. 5668-5681.

Research output: Contribution to journalArticle

Mummidi, S, Adams, LM, VanCompernolle, SE, Kalkonde, M, Camargo, JF, Kulkarni, H, Bellinger, AS, Bonello, G, Tagoh, H, Ahuja, SS, Unutmaz, D & Ahuja, SK 2007, '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', Journal of Immunology, vol. 178, no. 9, pp. 5668-5681.
Mummidi, Srinivas ; Adams, Lisa M. ; VanCompernolle, Scott E. ; Kalkonde, Mrunal ; Camargo, Jose F. ; Kulkarni, Hemant ; Bellinger, Adam S. ; Bonello, Gregory ; Tagoh, Hiromi ; Ahuja, Seema S ; Unutmaz, Derya ; Ahuja, Sunil K. / 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. In: Journal of Immunology. 2007 ; Vol. 178, No. 9. pp. 5668-5681.
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