title: Engagement of specific T-cell surface molecules regulates cytoskeletal polarization in HTLV-1-infected lymphocytes.
abstract: Cell-cell contact is required for efficient transmission of human T-lymphotropic virus type 1 (HTLV-1). An HTLV-1-infected cell polarizes its microtubule-organizing center (MTOC) toward the cell-cell junction; HTLV-1 core (Gag) complexes and the HTLV-1 genome accumulate at the point of contact and are then transferred to the uninfected cell. However, the mechanisms involved in this cytoskeletal polarization and transport of HTLV-1 complexes are unknown. Here, we tested the hypothesis that engagement of a specific T-cell surface ligand is synergistic with HTLV-1 infection in causing polarization of the MTOC to the cell contact region. We show that antibodies to intercellular adhesion molecule-1 (ICAM-1; CD54) caused MTOC polarization at a higher frequency in HTLV-1-infected cells. ICAM-1 is upregulated on HTLV-1-infected cells, and, in turn, ICAM-1 on the cell surface upregulates HTLV-1 gene expression. We propose that a positive feedback loop involving ICAM-1 and HTLV-1 Tax protein facilitates the formation of the virologic synapse and contributes to the T-cell tropism of HTLV-1. In contrast, MTOC polarization induced in T cells by antibodies to CD3 or CD28 was significantly inhibited by HTLV-1 infection.
authors.affiliation: Department of Immunology, Wright-Fleming Institute, Imperial College London, St Mary's Campus, London W2 1PG, United Kingdom.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Barnard
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Igakura
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Bangham
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000502:physiology* / Q000821:virology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D002450:Cell Communication; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism / Q000821:virology; D016356:Gene Products, tax / Q000502:physiology; D015490:HTLV-I Infections / Q000209:etiology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D022101:Microtubule-Organizing Center / Q000502:physiology / Q000821:virology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; D016356:Gene Products, tax; D018799:Intercellular Adhesion Molecule-1