Letter abstract
Nature Cell Biology 10, 211 - 219 (2008)
Published online: 13 January 2008 | doi:10.1038/ncb1682
Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission
Stefanie Sowinski1, Clare Jolly2, Otto Berninghausen1, Marco A. Purbhoo1, Anne Chauveau1, Karsten Köhler1, Stephane Oddos1, Philipp Eissmann1, Frances M. Brodsky3, Colin Hopkins1, Björn Önfelt4, Quentin Sattentau2 & Daniel M. Davis1
Transmission of HIV-1 via intercellular connections has been estimated as 100–1000 times more efficient than a cell-free process, perhaps in part explaining persistent viral spread in the presence of neutralizing antibodies1, 2. Such effective intercellular transfer of HIV-1 could occur through virological synapses3, 4, 5 or target-cell filopodia connected to infected cells6. Here we report that membrane nanotubes, formed when T cells make contact and subsequently part, provide a new route for HIV-1 transmission. Membrane nanotubes are known to connect various cell types, including neuronal and immune cells7, 8, 9, 10, 11, 12, 13, and allow calcium-mediated signals to spread between connected myeloid cells9. However, T-cell nanotubes are distinct from open-ended membranous tethers between other cell types7, 12, as a dynamic junction persists within T-cell nanotubes or at their contact with cell bodies. We also report that an extracellular matrix scaffold allows T-cell nanotubes to adopt variably shaped contours. HIV-1 transfers to uninfected T cells through nanotubes in a receptor-dependent manner. These data lead us to propose that HIV-1 can spread using nanotubular connections formed by short-term intercellular unions in which T cells specialize.
- Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, SW7 2AZ, UK.
- Sir William Dunn School of Pathology, University of Oxford, OX1 3RE, UK.
- The G. W. Hooper Foundation, Box 0552, 513 Parnassus Avenue, UCSF, San Francisco, CA 94143–0552, USA.
- Microbiology and Tumor Biology Center, Karolinska Institute, Box 280, S-171 77 Stockholm, Sweden.
Correspondence to: Daniel M. Davis1 e-mail: d.davis@imperial.ac.uk
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