Abstract
Human T-cell leukemia virus and simian T-cell leukemia virus (STLV) form the primate T-cell lymphotropic viruses group. Human T-cell leukemia virus type 1 and type 2 (HTLV-1 and HTLV-2) encode the Tax viral transactivator (Tax1 and Tax2, respectively). Tax1 possesses an oncogenic potential and is responsible for cell transformation both in vivo and in vitro. We and others have recently discovered the existence of human T-cell lymphotropic virus type 3. However, there is currently no evidence for the presence of a Tax protein in HTLV-3-infected individuals. We show that the serum of an HTLV-3 asymptomatic carrier and the sera of two STLV-3-infected monkeys contain specific anti-Tax3 antibodies. We also show that tax3 mRNA is present in the PBMCs obtained from an STLV-3-infected monkey, demonstrating that Tax3 is expressed in vivo. We further demonstrate that Tax3 intracellular localization is very similar to that of Tax1 and that Tax3 binds to both CBP and p300 coactivators. Using purified Tax3, we show that the protein increases transcription from a 4TxRE G-free cassette plasmid in an in vitro transcription assay. In all cell types tested, including transiently transfected lymphocytes, Tax3 activates its own promoter STLV-3 long terminal repeat (LTR), which contains only two Tax Responsive Elements (TREs), and activates also HTLV-1 and HTLV-2 LTRs. In addition, Tax3 also activates the NF-κB pathway. We also show that Tax3 possesses a PDZ-binding sequence at its C-terminal end. Our results demonstrate that Tax3 is a transactivator, and that its properties are more similar to that of Tax1, rather than of Tax2. This suggests the possible occurrence of lymphoproliferative disorders among HTLV-3-infected populations.
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Acknowledgements
This work was supported by a grant from l'Association de Recherche sur le Cancer (ARC #4781) to RM and fellowships from le Ministère de la Recherche to SAC and CANAM and Pasteur Weizmann to LM. It was also partially supported by grants from the George Washington University REF funds to AA and FK; NIH grants AI44357, AI43894 and 13969 to FK. RM is supported by INSERM. We thank Dr P Jalinot for the generous gift of the pSGF-cl.15 plasmid, Dr P Mauclère (Centre Pasteur du Cameroun), Dr J Fagot (CNRS) for their help in obtaining the monkeys blood samples and Dr A Froment (IRD) for his help in obtaining the blood sample of the HTLV-3-infected individual.
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Chevalier, S., Meertens, L., Pise-Masison, C. et al. The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax. Oncogene 25, 4470–4482 (2006). https://doi.org/10.1038/sj.onc.1209472
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DOI: https://doi.org/10.1038/sj.onc.1209472
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