Engagement of specific T-cell surface molecules regulates cytoskeletal polarization in HTLV-1–infected lymphocytes

• Published in: Blood 2005-08, Vol.106 (3), p.988-995
• Main Authors: Barnard, Amanda L., Igakura, Tadahiko, Tanaka, Yuetsu, Taylor, Graham P., Bangham, Charles R.M.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; CD4-Positive T-Lymphocytes - chemistry; CD4-Positive T-Lymphocytes - physiology; CD4-Positive T-Lymphocytes - virology; Cell Adhesion Molecules - physiology; Cell Communication; Cell Polarity - physiology; Cells, Cultured; Cytoskeleton - metabolism; Cytoskeleton - virology; Gene Products, tax - physiology; HTLV-I Infections - etiology; Human T-lymphotropic virus 1 - genetics; Human T-lymphotropic virus 1 - physiology; Human viral diseases; Humans; Infectious diseases; Intercellular Adhesion Molecule-1 - biosynthesis; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - physiology; Medical sciences; Microtubule-Organizing Center - physiology; Microtubule-Organizing Center - virology; Up-Regulation - genetics; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2004-07-2850

Cell-cell contact is required for efficient transmission of human T-lymphotropic virus type 1 (HTLV-910101). 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.