Letter | Published:

Retroviruses can establish filopodial bridges for efficient cell-to-cell transmission

Nature Cell Biology volume 9, pages 310315 (2007) | Download Citation

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Abstract

The spread of retroviruses between cells is estimated to be 2–3 orders of magnitude more efficient when cells can physically interact with each other1,2. The underlying mechanism is largely unknown, but transfer is believed to occur through large-surface interfaces, called virological or infectious synapses3,4,5,6. Here, we report the direct visualization of cell-to-cell transmission of retroviruses in living cells. Our results reveal a mechanism of virus transport from infected to non-infected cells, involving thin filopodial bridges. These filopodia originate from non-infected cells and interact, through their tips, with infected cells. A strong association of the viral envelope glycoprotein (Env) in an infected cell with the receptor molecules in a target cell generates a stable bridge. Viruses then move along the outer surface of the filopodial bridge toward the target cell. Our data suggest that retroviruses spread by exploiting an inherent ability of filopodia to transport ligands from cell to cell.

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Acknowledgements

We are grateful to T. Rapoport for his support. We thank Z. Jiang for assistance with scanning electron microscopy, and P. Uchil and J. Jin for critical reading of the manuscript. This work was supported by National Institutes of Health (NIH) grants R01CA098727 and R21 AI065284, as well as the Searle Scholars Program to W.M., and a Leopoldina Fellowship BMBF-LPD 9901/8-75 to M.L.

Author information

Author notes

    • Nathan M. Sherer

    Current address: Department of Infectious Diseases, King's College London School of Medicine, London Bridge, London, SE1 9RT, UK.

    • Maik J. Lehmann

    Current address: Department of Virology, Hygiene Institute, University of Heidelberg Medical School, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.

    • Luisa F. Jimenez-Soto

    Current address: Max-von-Pettenkofer Institute, LMU Munich, Pettenkoferstrasse 9a, 80336 Munich, Germany

Affiliations

  1. Section of Microbial Pathogenesis, Yale University School of Medicine, 295 Congress Ave, New Haven, CT 06536, USA.

    • Nathan M. Sherer
    • , Maik J. Lehmann
    • , Luisa F. Jimenez-Soto
    •  & Walther Mothes
  2. Department of Cell Biology, Yale University School of Medicine, 295 Congress Ave, New Haven, CT 06536, USA.

    • Christina Horensavitz
    •  & Marc Pypaert

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Contributions

N.M.S, with support from M.J.L, L.F.J.-S. and W.M. were responsible for the experimental work. C.H. and M.P. performed transmission electron microscopy. W.M. and N.M.S. were involved in project planning, data analysis and writing.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Walther Mothes.

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DOI

https://doi.org/10.1038/ncb1544

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