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J. Biol. Chem., Vol. 280, Issue 33, 29653-29660, August 19, 2005

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Human T-lymphotropic Virus, Type 1, Tax Protein Triggers Microtubule Reorientation in the Virological Synapse^*

Mohamed Nejmeddine, Amanda L. Barnard, Yuetsu Tanaka, Graham P. Taylor¶, and Charles R. M. Bangham||

From the Department of Immunology and the ^¶Department of Infectious Diseases, Wright-Fleming Institute, Imperial College, St Mary's Campus, Norfolk Place, W2 1PG, London, United Kingdom and the Department of Immunology, Graduate School and Faculty of Medicine, University of Ryukyus, Uehara-cho 207, Nishihara-cho, Nakagami-gun, Okinawa 903-0215, Japan

We showed recently that the human T-lymphotropic virus, type 1 (HTLV-1), spreads directly from cell to cell via a virological synapse. The HTLV-1 virological synapse resembles the immunological synapse; each is a specialized contact between a lymphocyte and another cell that contains organized protein microdomains, and each involves repolarization of the T-cell microtubule cytoskeleton. However, formation of the virological synapse is not triggered by T-cell receptor-mediated antigen recognition. On the basis of our previous data, we postulated that formation of the viral synapse was triggered by a conjunction of two signals, one from HTLV-1 infection of the T-cell and one from cell-cell contact. We have recently identified ICAM-1 engagement as a cell-contact signal that causes the microtubule polarization associated with the virological synapse. Here we used confocal microscopy of T-lymphocytes naturally infected with HTLV-1 or transfected with individual HTLV-1 genes to investigate the role of the viral transcriptional transactivator protein Tax. Polarization of the microtubules was induced by cell-cell contact or by cross-linking T-cell surface molecules with monoclonal antibodies adsorbed to latex beads. We show that Tax, which is mainly found in the nucleus, is also present at two specific extranuclear sites as follows: around the microtubule organizing center in association with the cis-Golgi and in the cell-cell contact region. We show that expression of Tax provides an intracellular signal that synergizes with ICAM-1 engagement to cause the T-cell microtubule polarization observed at the virological synapse.

Received for publication, March 10, 2005 , and in revised form, June 13, 2005.

^* This work was supported by the Wellcome Trust (UK) and the Leukemia Research Fund, UK. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains Figs. S1–S3.

^|| To whom correspondence should be addressed: Dept. of Immunology, Wright-Fleming Institute, Imperial College, St. Mary's Campus, Norfolk Place, London W2 1PG, UK. Tel.: 44-20-7594-3730; Fax: 44-20-7402-0653; E-mail: c.bangham{at}imperial.ac.uk.

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