Cited by 762HIV Research and TreatmentCellular transport and secretionExtracellular vesicles in disease

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

Sowinski, Stefanie, Jolly, Clare, Berninghausen, Otto, Purbhoo, Marco A., Chauveau, Anne, Köhler, Karsten, Oddos, Stephane, Eissmann, Philipp +5 more·2008·Nature Cell Biology

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.

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Crossref · 10.1038/ncb1682

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Authors
Sowinski, S., Jolly, C., Berninghausen, O., Purbhoo, M. A., Chauveau, A., Köhler, K., Oddos, S., Eissmann, P., Brodsky, F. M., Hopkins, C., Önfelt, B., Sattentau, Q., & Davis, D. M.
Affiliations
  • Imperial College London (GB)
  • University of Oxford (GB)
  • University of California, San Francisco (US)
  • Karolinska Institutet (SE)
Corresponding author
Davis, Daniel M.
Venue
Nature Cell Biology
Published
2008-01-13
Volume
10
Issue
2
Pages
211-219
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
OpenAlex
W2088757776
Cited by
754
References
31
Citations by year
2026: 22 · 2025: 19 · 2024: 30 · 2023: 24 · 2022: 38 · 2021: 45 · 2020: 47 · 2019: 37 · 2018: 46 · 2017: 41 · 2016: 48 · 2015: 35 · 2014: 38 · 2013: 32 · 2012: 58
FWCI
20.05
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Wellcome Trust
  • Biotechnology and Biological Sciences Research Council (BB/D011663/1)
  • National Institute of Allergy and Infectious Diseases (P01AI064520)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Keywords
tunneling nanotubes, HIV-1 transmission, T cells, cell-cell contact, virological synapse, extracellular matrix scaffolds, calcium signaling
MeSH terms
Humans, Intercellular Junctions, T-Lymphocytes, Virulence, HIV-1, Jurkat Cells, Cell Surface Extensions

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