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Journal of Virology, October 2006, p. 9876-9888, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.00799-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Human T-Cell Lymphotropic Virus Type 3: Complete Nucleotide Sequence and Characterization of the Human Tax3 Protein

Sara Calattini,^1, Sébastien Alain Chevalier,^1, Renan Duprez,¹ Philippe Afonso,¹ Alain Froment,² Antoine Gessain,¹ and Renaud Mahieux^1*

Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, CNRS URA 1930, Département de Virologie, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris, France,¹ Laboratoire ERMES, IRD, Technoparc, Orléans cedex 2, France²

Received 19 April 2006/ Accepted 6 July 2006

We and others have recently uncovered the existence of human T-cell lymphotropic virus type 3 (HTLV-3), the third member of the HTLV family. We have now sequenced the full-length HTLV-3_Pyl43 provirus. As expected, HTLV-3_Pyl43 contains open reading frames corresponding to the gag, pol, env, tax, and rex genes. Interestingly, its long terminal repeat (LTR) includes only two Tax-responsive elements, as is the case for type 3 simian T-cell lymphotropic viruses (STLV-3). Phylogenetic analyses reveal that HTLV-3_Pyl43 is closely related to central African STLV-3. Unexpectedly, the proximal pX region of HTLV-3_Pyl43 lacks 366 bp compared to its STLV-3 counterpart. Because of this deletion, the previously described RorfII sequence is lacking. At the amino acid level, Tax3_Pyl43 displays strong similarities with HTLV-1 Tax, including the sequence of a PDZ class I binding motif. In transient-transfection assays, Tax3_Pyl43 activates the transcriptions from HTLV-3, HTLV-1, and HTLV-2 LTRs. Mutational analysis indicates that two functional domains (M22 and M47) important for transactivation through the CREB/ATF or NF-B pathway are similar but not identical in Tax1 and Tax3_Pyl43. We also show that Tax3_Pyl43 transactivates the human interleukin-8 and Bcl-X_L promoters through the induction of the NF-B pathway. On the other hand, Tax3_Pyl43 represses the transcriptional activity of the p53 tumor suppressor protein as well as the c-Myb promoter. Altogether, these results demonstrate that although HTLV-3 and HTLV-1 have only 60% identity, Tax3_Pyl43 is functionally closely related to the transforming protein Tax1 and suggest that HTLV-3, like HTLV-1, might be pathogenic in vivo.

Supplemental material for this article may be found at http://jvi.asm.org/.

These authors contributed equally to this work.

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