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Journal of Virology, January 2007, p. 301-308, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.00766-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Human T-Cell Leukemia Virus Type 1 Tax Protein Down-Regulates Pre-T-Cell Receptor Alpha Gene Transcription in Human Immature Thymocytes{triangledown}

Mélanie Wencker,1 Céline Sausse,1 David Derse,2 Louis Gazzolo,1 and Madeleine Duc Dodon1*

INSERM-U758, Virologie Humaine, Ecole Normale Supérieure de Lyon, IFR 128 BioSciences, Lyon-Gerland, 46, Allée d'Italie 69364, Lyon Cedex 07, France,1 HIV Drug Resistance Program, Center for Cancer Research, National Cancer Institute—Frederick, Frederick, Maryland 21702-12012

Received 14 April 2006/ Accepted 8 October 2006

The human pre-T-cell receptor alpha (TCR{alpha}; pT{alpha}) gene encodes a polypeptide which associates with the TCRß chain and CD3 molecules to form the pre-TCR complex. The surface expression of the pre-TCR is pT{alpha} dependent, and signaling through this complex triggers an early {alpha}ß T-cell developmental checkpoint inside the thymus, known as ß-selection. E2A transcription factors, which are involved at multiple stages of T-cell development, regulate the transcription of the pT{alpha} gene. Here we show that the regulatory protein Tax of the human T-cell leukemia virus type 1 (HTLV-1) efficiently suppresses the E47-mediated activation of the pT{alpha} promoter. Furthermore, we report that in Tax lentivirally transduced human MOLT-4 T cells, which constitutively express the pT{alpha} gene, the amount of pT{alpha} transcripts decreases. Such a decrease is not observed in MOLT-4 cells transduced by a vector encoding the Tax mutant K88A, which is unable to interact with p300. These data underline that Tax inhibits pT{alpha} transcription by recruiting this coactivator. Finally, we show that the expression of Tax in human immature thymocytes results in a decrease of pT{alpha} gene transcription but does not modify the level of E47 transcripts. These observations indicate that Tax, by silencing E proteins, down-regulates pT{alpha} gene transcription during early thymocyte development. They further provide evidence that Tax can interfere with an important checkpoint during T-cell differentiation in the thymus.

* Corresponding author. Mailing address: Virologie Humaine U758, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon Cedex 07, France. Phone: 33 (0) 4 72 72 89 62. Fax: 33 (0) 4 72 72 81 37. E-mail: madeleine.duc.dodon{at}ens-lyon.fr.

{triangledown} Published ahead of print on 18 October 2006.

Journal of Virology, January 2007, p. 301-308, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.00766-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Terme, J.-M., Wencker, M., Favre-Bonvin, A., Bex, F., Gazzolo, L., Duc Dodon, M., Jalinot, P. (2008). Cross Talk between Expression of the Human T-Cell Leukemia Virus Type 1 Tax Transactivator and the Oncogenic bHLH Transcription Factor TAL1. J. Virol. 82: 7913-7922 [Abstract] [Full Text]  


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