Human T-lymphotropic virus, type 1, tax protein triggers microtubule reorientation in the virological synapse.
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.
Department of Immunology, Wright-Fleming Institute, Imperial College, St Mary's Campus, London, UK.
Mohamed
M
Nejmeddine
Amanda L
AL
Barnard
Yuetsu
Y
Tanaka
Graham P
GP
Taylor
Charles R M
CR
Bangham
D008841:Actin Cytoskeleton / Q000502:physiology; D002450:Cell Communication; D016764:Cell Polarity; D016356:Gene Products, tax / Q000032:analysis / Q000502:physiology*; D006056:Golgi Apparatus / Q000737:chemistry; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D007365:Intercellular Junctions / Q000821:virology*; D022101:Microtubule-Organizing Center / Q000737:chemistry / Q000502:physiology; D008870:Microtubules / Q000502:physiology*; D013601:T-Lymphocytes / Q000821:virology*
D016356:Gene Products, tax