| Autor: |
Steven M. Wolinsky, Carole Equeter, M Ravoet, Haidar Akl, Arsène Burny, G Dorbrita, Jennifer Stanton, Kevin J. Kunstman, Germain Manfouo-Foutsop, Bassam Badran, Karen Willard-Gallo |
| Rok vydání: |
2005 |
| Předmět: |
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| Zdroj: |
Retrovirology, Vol 2, Iss Suppl 1, p S113 (2005) |
| ISSN: |
1742-4690 |
| DOI: |
10.1186/1742-4690-2-s1-s113 |
| Popis: |
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 CD3e 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. from 2005 International Meeting of The Institute of Human Virology Baltimore, USA, 29 August – 2 September 2005 |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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