Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission.
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.
Sowinski
Stefanie
S
Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, SW7 2AZ, UK.
Jolly
Clare
C
Berninghausen
Otto
O
Purbhoo
Marco A
MA
Chauveau
Anne
A
Köhler
Karsten
K
Oddos
Stephane
S
Eissmann
Philipp
P
Brodsky
Frances M
FM
Hopkins
Colin
C
Onfelt
Björn
B
Sattentau
Quentin
Q
Davis
Daniel M
DM
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