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  • Oral presentation
  • Open Access

Targeting the Human CD3γ Gene Promoter By HIV-1 and HTLV-1: Two Distinct Mechanisms Involving A Transcriptional Regulatory Element and Chromatin Remodeling

  • 1Email author,
  • 1,
  • 1,
  • 1,
  • 1,
  • 1,
  • 1,
  • 1,
  • 2,
  • 2 and
  • 2
Retrovirology20052 (Suppl 1) :S113

https://doi.org/10.1186/1742-4690-2-S1-S113

  • Published:

Keywords

  • Chromatin Remodel
  • Transcriptional Regulatory Element
  • Inhibitor Trichostatin
  • Specific Nuclear Protein
  • EMSA Experiment

Our studies show that HIV-1, HIV-2, and HTLV-I infection all provoke a progressive defect in surface T cell receptor expression. A specific loss of CD3γ transcripts is responsible for the defect after HIV-1 or HIV-2 infection. Alternatively, while CD3γ transcripts are lost first after HTLV-I infection, their reduction is followed several months later by a loss of CD3δ and subsequently CD3ε mRNA. Studies of CD3γ transcriptional control revealed parallels with elements regulating HIV-1 gene expression, including a downstream element reminiscent of HIV TAR. Mutant and deletion CD3γ promoter constructs delimited a 53 bp region downstream from the major transcription start site as critical for positive gene expression. EMSA experiments demonstrate that this sequence functions through an RNA rather than a DNA intermediate, which can bind three specific nuclear protein complexes. Deletion of U at +9 and +37 kills promoter activity. Alternatively, progressive silencing of the CD3 gene locus by HTLV-I functions via chromatin remodeling, characterized by increased binding of Ikaros to the CD3 γ promoter and the CD3δ enhancer. Expression of the CD3 genes can be reactivated in HTLV-I infected cells by the synergistic action of the histone deactylase inhibitor trichostatin A and the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine. The importance of viral targeting of the CD3 genes will be discussed.

Notes

Authors’ Affiliations

(1)
University of Brussels (ULB), Bordet Institute, Brussels, Belgium
(2)
Northwestern University Medical School, Chicago, IL, USA

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