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.
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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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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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DOI: https://doi.org/10.1038/ncb1544
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