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Journal of Virology, December 2002, p. 12813-12822, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12813-12822.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Complementary Strand of the Human T-Cell Leukemia Virus Type 1 RNA Genome Encodes a bZIP Transcription Factor That Down-Regulates Viral Transcription

Gilles Gaudray, Frederic Gachon,{dagger} Jihane Basbous, Martine Biard-Piechaczyk, Christian Devaux, and Jean-Michel Mesnard*

Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CNRS/UM I UMR 5121, Institut de Biologie, 34060 Montpellier, France

Received 27 March 2002/ Accepted 5 September 2002

The RNA genome of the human T-cell leukemia virus type 1 (HTLV-1) codes for proteins involved in infectivity, replication, and transformation. We report in this study the characterization of a novel viral protein encoded by the complementary strand of the HTLV-1 RNA genome. This protein, designated HBZ (for HTLV-1 bZIP factor), contains a N-terminal transcriptional activation domain and a leucine zipper motif in its C terminus. We show here that HBZ is able to interact with the bZIP transcription factor CREB-2 (also called ATF-4), known to activate the HTLV-1 transcription by recruiting the viral trans-activator Tax on the Tax-responsive elements (TxREs). However, we demonstrate that the HBZ/CREB-2 heterodimers are no more able to bind to the TxRE and cyclic AMP response element sites. Taking these findings together, the functional inactivation of CREB-2 by HBZ is suggested to contribute to regulation of the HTLV-1 transcription. Moreover, the characterization of a minus-strand gene protein encoded by HTLV-1 has never been reported until now.

* Corresponding author. Mailing address: Laboratoire Infections Rétrovirales et Signalisation Cellulaire, Institut de Biologie, 4 Bd Henri IV, 34060 Montpellier, France. Phone: (33) 4 67 60 86 60. Fax: (33) 4 67 60 44 20. E-mail: mesnard{at}crbm.cnrs-mop.fr.

{dagger} Present address: Department of Molecular Biology, Sciences II, University of Geneva, CH-1211 Geneva-4, Switzerland.

Journal of Virology, December 2002, p. 12813-12822, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12813-12822.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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