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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{dagger}

Sara Calattini,1,{ddagger} Sébastien Alain Chevalier,1,{ddagger} Renan Duprez,1 Philippe Afonso,1 Alain Froment,2 Antoine Gessain,1 and Renaud Mahieux1*

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-3Pyl43 provirus. As expected, HTLV-3Pyl43 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-3Pyl43 is closely related to central African STLV-3. Unexpectedly, the proximal pX region of HTLV-3Pyl43 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, Tax3Pyl43 displays strong similarities with HTLV-1 Tax, including the sequence of a PDZ class I binding motif. In transient-transfection assays, Tax3Pyl43 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-{kappa}B pathway are similar but not identical in Tax1 and Tax3Pyl43. We also show that Tax3Pyl43 transactivates the human interleukin-8 and Bcl-XL promoters through the induction of the NF-{kappa}B pathway. On the other hand, Tax3Pyl43 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, Tax3Pyl43 is functionally closely related to the transforming protein Tax1 and suggest that HTLV-3, like HTLV-1, might be pathogenic in vivo.

* Corresponding author. Mailing address: Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, CNRS URA 1930, Département de Virologie, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris cedex 15, France. Phone: (33)-1-45-68-89-06. Fax: (33)-1-40-61-34-65. E-mail: rmahieux{at}pasteur.fr.

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

{ddagger} These authors contributed equally to this work.

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.



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