Differences in the ability of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 tax to inhibit p53 function

Renaud Mahieux, Cynthia A. Pise-Masison, Paul F. Lambert, Christophe Nicot, Laura De Marchis, Antoine Gessain, Patrick Green, William Hall, John N. Brady

Research output: Contribution to journalArticle

Abstract

We have analyzed the functional activity of the p53 tumor suppressor in human T-cell lymphotropic virus type 2 (HTLV-2)-transformed cells. Abundant levels of the p53 protein were detected in both HTLV-2A and -2B virus- infected cell lines. The p53 was functionally inactive, however, both in transient-transfection assays using a p53 reporter plasmid and in induction of p53-responsive genes in response to gamma irradiation. We further investigated HTLV-2A Tax and HTLV-2B Tax effects on p53 activity. Interestingly, although Tax-2A and -2B inactivate p53, the Tax-2A protein appears to inhibit p53 function less efficiently than either Tax-1 or Tax-2B. In transient-cotransfection assays, Tax-1 and Tax-2B inactivated p53 by 80%, while Tax2A reduced p53 activity by 20%. In addition, Tax-2A does not increase the steady-state level of cellular p53 as well as Tax-1 or -2B does in the same assays. Cotransfection assays demonstrated that Tax-2A could efficiently transactivate CREB-responsive promoters to the same level as Tax- 1 and Tax-2B, indicating that the protein was functional. This report provides evidence of the first functional difference between the HTLV-2A and -2B subtypes. This comparison of the action of HTLV-1 and HTLV-2 Tax proteins on p53 function will provide important insights into the mechanism of HTLV transformation.

Original languageEnglish
Pages (from-to)6866-6874
Number of pages9
JournalJournal of Virology
Volume74
Issue number15
DOIs
Publication statusPublished - Aug 2000

ASJC Scopus subject areas

  • Immunology

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    Mahieux, R., Pise-Masison, C. A., Lambert, P. F., Nicot, C., De Marchis, L., Gessain, A., Green, P., Hall, W., & Brady, J. N. (2000). Differences in the ability of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 tax to inhibit p53 function. Journal of Virology, 74(15), 6866-6874. https://doi.org/10.1128/JVI.74.15.6866-6874.2000