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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

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; pT) 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 dependent, and signaling through this complex triggers an early 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 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 promoter. Furthermore, we report that in Tax lentivirally transduced human MOLT-4 T cells, which constitutively express the pT gene, the amount of pT 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 transcription by recruiting this coactivator. Finally, we show that the expression of Tax in human immature thymocytes results in a decrease of pT gene transcription but does not modify the level of E47 transcripts. These observations indicate that Tax, by silencing E proteins, down-regulates pT 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.

Published ahead of print on 18 October 2006.

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