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

Nature Cell Biology volume 9, pages 310–315 (2007)Cite this article

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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Figure 1: MLV moves from cell-to-cell along filopodial bridges.
Figure 2: Viruses move along the outer surface of filopodial bridges toward target cells.
Figure 3: Viral cytoneme formation depends on Env–receptor interactions.
Figure 4: Viral cytoneme formation is driven by endocytic forces in the infected cell.
Figure 5: Cytonemes mediate cell-to-cell transmission of retroviruses.

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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.

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Author notes

  1. Nathan M. Sherer

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

  2. Maik J. Lehmann

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

  3. Luisa F. Jimenez-Soto

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

Authors and Affiliations

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

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Correspondence to Walther Mothes.

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Sherer, N., Lehmann, M., Jimenez-Soto, L. et al. Retroviruses can establish filopodial bridges for efficient cell-to-cell transmission. Nat Cell Biol 9, 310–315 (2007). https://doi.org/10.1038/ncb1544

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