Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission

Nat Cell Biol. 2008 Feb;10(2):211-9. doi: 10.1038/ncb1682. Epub 2008 Jan 13.

Abstract

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 antibodies. Such effective intercellular transfer of HIV-1 could occur through virological synapses or target-cell filopodia connected to infected cells. 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 cells, and allow calcium-mediated signals to spread between connected myeloid cells. However, T-cell nanotubes are distinct from open-ended membranous tethers between other cell types, 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Surface Extensions / physiology*
  • Cell Surface Extensions / ultrastructure
  • HIV-1 / physiology*
  • Humans
  • Intercellular Junctions / physiology*
  • Intercellular Junctions / ultrastructure
  • Jurkat Cells
  • T-Lymphocytes / physiology*
  • T-Lymphocytes / ultrastructure
  • T-Lymphocytes / virology
  • Virulence