Submitted on November 4, 2002
Accepted on January 28, 2003
Spread of HTLV-I Between Lymphocytes by Virus-Induced Polarization of the Cytoskeleton
Tadahiko Igakura 1,
Jane C. Stinchcombe 2,
Peter K. C. Goon 3,
Graham P. Taylor 4,
Jonathan N. Weber 4,
Gillian M. Griffiths 2,
Yuetsu Tanaka 5,
Mitsuhiro Osame 6,
Charles R. M. Bangham 3*
1 Department of Immunology, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, UK; The Third Department of Internal Medicine, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
2 Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
3 Department of Immunology, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, UK.
4 Department of Genito-Urinary Medicine and Communicable Diseases, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, UK.
5 Department of Infectious Disease and Immunology, Okinawa-Asia Research Center of Medical Science, Faculty of Medicine, University of the Ryukyus, Uehara-cho 207, Nishihara, Okinawa 903-0215, Japan.
6 The Third Department of Internal Medicine, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
* To whom correspondence should be addressed. E-mail: [email protected].
Cell contact is required for efficient transmission of human T-lymphotropic virus type 1 (HTLV-I) between cells and between individuals, because naturally infected lymphocytes produce virtually no cell-free infectious HTLV-I particles. However, the mechanism of cell-to-cell spread of HTLV-I is not understood. We show here that cell contact rapidly induces polarization of the cytoskeleton of the infected cell to the cell-cell junction. HTLV-I core (Gag protein) complexes and the HTLV-I genome accumulate at the cell-cell junction and are then transferred to the uninfected cell. Other lymphotropic viruses, such as HIV-1, may similarly subvert normal T-cell physiology to allow efficient propagation between cells.