title: Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission.
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.
authors.affiliation: Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, SW7 2AZ, UK.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Sowinski
authors.forename: Clare
authors.initials: C
authors.lastname: Jolly
authors.forename: Otto
authors.initials: O
authors.lastname: Berninghausen
authors.forename: Marco A
authors.initials: MA
authors.lastname: Purbhoo
authors.forename: Anne
authors.initials: A
authors.lastname: Chauveau
authors.forename: Karsten
authors.initials: K
authors.lastname: Köhler
authors.forename: Stephane
authors.initials: S
authors.lastname: Oddos
authors.forename: Philipp
authors.initials: P
authors.lastname: Eissmann
authors.forename: Frances M
authors.initials: FM
authors.lastname: Brodsky
authors.forename: Colin
authors.initials: C
authors.lastname: Hopkins
authors.forename: Björn
authors.initials: B
authors.lastname: Onfelt
authors.forename: Quentin
authors.initials: Q
authors.lastname: Sattentau
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Davis
mesh_terms: D022081:Cell Surface Extensions / Q000502:physiology* / Q000648:ultrastructure; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology* / Q000648:ultrastructure; D019169:Jurkat Cells; D013601:T-Lymphocytes / Q000502:physiology* / Q000648:ultrastructure / Q000821:virology; D014774:Virulence