Retroviruses can establish filopodial bridges for efficient cell-to-cell transmission
Open accessAbstract
The spread of retroviruses between cells is estimated to be 2-3 orders of magnitude more efficient when cells can physically interact with each other. The underlying mechanism is largely unknown, but transfer is believed to occur through large-surface interfaces, called virological or infectious synapses. 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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Cytonemes form between retrovirus-infected and uninfected cells, mediated by Env-viral receptor interaction; budding viral particles surf along cytonemes toward the target cell using actin-myosin cytoskeleton.
“Subsequently, these authors observed the formation of filopodia bridges (cytonemes) between retrovirus-infected and uninfected cells [105]. Cytonemes extended from the uninfected cell, and connected to the surface of the infected cell, a phenomenon mediated by the interaction of an Env with a viral receptor. The budding viral particles “surfed” along the cytonemes and towards the target cell using”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [105]
Viruses have evolved several mechanisms, including cell-cell fusion, synapse formation, actin tails, filopodial bridges, and nanotubes, to facilitate secure and rapid cell-to-cell dissemination.
“Viruses have evolved several mechanisms, including cell-cell fusion, synapse formation, and induction of actin tails, filopodial bridges, or nanotubes, and are equipped with the necessary information to facilitate a secure and rapid cell-to-cell dissemination (Aubert et al., 2009; Bennett et al., 2009; Sherer et al., 2007; Sowinski et al., 2008).”
From Equid Herpesvirus-1 Exploits the Extracellular Matrix of Mononuclear Cells to Ensure Transport to Target Cells (2020) · cites this paper as Sherer et al., 2007
Cites
Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER
Pelkmans, L., Kartenbeck, J., & Helenius, A. (2001) · Nature Cell Biology · doi:10.1038/35074539 · Cited by 1,236 · see citing works
Evidence for a Role of Dendritic Filopodia in Synaptogenesis and Spine Formation
Ziv, N. E., & Smith, S. J. (1996) · Neuron · doi:10.1016/s0896-6273(00)80283-4 · Cited by 863 · see citing works
Two Distinct Actin Networks Drive the Protrusion of Migrating Cells
Ponti, A., Macháček, M., Gupton, S. L., Waterman, C. M., & Danuser, G. M. (2004) · Science · doi:10.1126/science.1100533 · Cited by 820 · see citing works
Spread of HTLV-I Between Lymphocytes by Virus-Induced Polarization of the Cytoskeleton
Igakura, T., Stinchcombe, J. C., Goon, P. K. C., Taylor, G. P., Weber, J. N., Griffiths, G. M., Tanaka, Y., Osame, M., & Bangham, C. R. M. (2003) · Science · doi:10.1126/science.1080115 · Cited by 755 · see citing works
Recruitment of HIV and Its Receptors to Dendritic Cell-T Cell Junctions
McDonald, D., Wu, L., Bohks, S. M., KewalRamani, V. N., Unutmaz, D., & Hope, T. J. (2003) · Science · doi:10.1126/science.1084238 · Cited by 707 · see citing works
HIV-1 Cell to Cell Transfer across an Env-induced, Actin-dependent Synapse
Jolly, C., Kashefi, K., Hollinshead, M., & Sattentau, Q. J. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20030648 · Cited by 623 · see citing works
Ramı́rez-Weber, F.-A., & Kornberg, T. B. (1999) · Cell · doi:10.1016/s0092-8674(00)80771-0 · Cited by 614 · see citing works
Quantitation of human immunodeficiency virus type 1 infection kinetics
Dimitrov, D. S., Willey, R. L., Sato, H., Chang, L. J., Blumenthal, R., & Martin, M. A. (1993) · Journal of Virology · doi:10.1128/jvi.67.4.2182-2190.1993 · Cited by 515 · see citing works
Önfelt, B., Nedvetzki, S., Benninger, R. K. P., Purbhoo, M. A., Sowinski, S., Hume, A. N., Seabra, M. C., Neil, M. A. A., French, P. M. W., & Davis, D. M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.12.8476 · Cited by 492 · see citing works
In vivo imaging of synapse formation on a growing dendritic arbor
Niell, C. M., Meyer, M. P., & Smith, S. J. (2004) · Nature Neuroscience · doi:10.1038/nn1191 · Cited by 441 · see citing works
Visualization of Retroviral Replication in Living Cells Reveals Budding into Multivesicular Bodies
Sherer, N. M., Lehmann, M. J., Soto, L. F. J., Ingmundson, A., Horner, S. M., Cicchetti, G., Allen, P. G., Pypaert, M., Cunningham, J. M., & Mothes, W. (2003) · Traffic · doi:10.1034/j.1600-0854.2003.00135.x · Cited by 411 · see citing works
Self-citationActin- and myosin-driven movement of viruses along filopodia precedes their entry into cells
Lehmann, M. J., Sherer, N. M., Marks, C. B., Pypaert, M., & Mothes, W. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200503059 · Cited by 403 · see citing works
Self-citationFunctional Connectivity between Immune Cells Mediated by Tunneling Nanotubules
Watkins, S. C., & Salter, R. D. (2005) · Immunity · doi:10.1016/j.immuni.2005.08.009 · Cited by 400 · see citing works
A receptor for subgroup A Rous sarcoma virus is related to the low density lipoprotein receptor
Bates, P., Young, J. A. T., & Varmus, H. E. (1993) · Cell · doi:10.1016/0092-8674(93)90726-7 · Cited by 355 · see citing works
A Functional Link between Dynamin and the Actin Cytoskeleton at Podosomes
Ochoa, G.-C., Slepnev, V. I., Neff, L., Ringstad, N., Takei, K., DANIELL, L. W., Kim, W., Cao, H., McNiven, M. A., Baron, R., et al. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.150.2.377 · Cited by 354 · see citing works
Retroviral entry mediated by receptor priming and low pH triggering of an envelope glycoprotein
Mothes, W., Boerger, A. L., Narayan, S., Cunningham, J. M., & Young, J. A. T. (2000) · Cell · doi:10.1016/s0092-8674(00)00170-7 · Cited by 288 · see citing works
Self-citationMIXED CULTURE CYTOPATHOGENICITY: A NEW TEST FOR GROWTH OF MURINE LEUKEMIA VIRUSES IN TISSUE CULTURE
Klement, V., Rowe, W. P., Hartley, J. W., et al. (1969) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.63.3.753 · Cited by 265 · see citing works
Dependence of Drosophila wing imaginal disc cytonemes on Decapentaplegic
Hsiung, F., Ramı́rez-Weber, F.-A., Iwaki, D. D., & Kornberg, T. B. (2005) · Nature · doi:10.1038/nature03951 · Cited by 216 · see citing works
Delta-promoted filopodia mediate long-range lateral inhibition in Drosophila
de Joussineau, C., Soule, J. D., Martin, M., Anguille, C., Montcourrier, P., & Alexandre, D. (2003) · Nature · doi:10.1038/nature02157 · Cited by 184 · see citing works
Carr, J. M., Hocking, H., Li, P., & Burrell, C. J. (1999) · Virology · doi:10.1006/viro.1999.0047 · Cited by 177 · see citing works
Gupta, N., & DeFranco, A. L. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.02-05-0078 · Cited by 170 · see citing works
Alfsen, A., Yu, H., Magérus, A., Schmitt, A., & Bomsel, M. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-03-0192 · Cited by 127 · see citing works
Imaging individual retroviral fusion events: From hemifusion to pore formation and growth
Melikyan, G. B., Barnard, R. J. O., Abrahamyan, L. G., Mothes, W., & Young, J. A. T. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501864102 · Cited by 94 · see citing works
Self-citationIdentification of a Receptor-Binding Pocket on the Envelope Protein of Friend Murine Leukemia Virus
Davey, R. A., Zuo, Y., & Cunningham, J. M. (1999) · Journal of Virology · doi:10.1128/jvi.73.5.3758-3763.1999 · Cited by 69 · see citing works
Zavorotinskaya, T., Qian, Z., Franks, J., & Albritton, L. M. (2003) · Journal of Virology · doi:10.1128/jvi.78.1.473-481.2004 · Cited by 42 · see citing works
Chen, C., Weisz, O. A., Stolz, D. B., Watkins, S. C., & Montelaro, R. C. (2003) · Journal of Virology · doi:10.1128/jvi.78.2.882-891.2004 · Cited by 33 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Sowinski, S., Jolly, C., Berninghausen, O., Purbhoo, M. A., Chauveau, A., Köhler, K., Oddos, S., Eissmann, P., Brodsky, F. M., Hopkins, C., et al. (2008) · Nature Cell Biology · doi:10.1038/ncb1682 · Cited by 754 · see citing works
Avoiding the void: Cell-to-cell spread of human viruses
Sattentau, Q. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1972 · Cited by 614 · see citing works
M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex
Hase, K., Kimura, S., Takatsu, H., Ohmae, M., Kawano, S., Kitamura, H., Ito, M., Watarai, H., Hazelett, C. C., Yeaman, C., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1990 · Cited by 402 · see citing works
Virus cell-to-cell transmission
Mothes, W., Sherer, N. M., Jin, J., & Zhong, P. (2010) · Journal of Virology · doi:10.1128/jvi.00443-10 · Cited by 353 · see citing works
Self-citationXu, W., Santini, P. A., Sullivan, J. S., He, B., Shan, M., Ball, S. C., Dyer, W. B., Ketas, T. J., Chadburn, A., Cohen-Gould, L., et al. (2009) · Nature Immunology · doi:10.1038/ni.1753 · Cited by 302 · see citing works
Cell-to-cell transmission of viruses
Zhong, P., Agosto, L. M., Munro, J. B., & Mothes, W. (2013) · Current Opinion in Virology · doi:10.1016/j.coviro.2012.11.004 · Cited by 231 · see citing works
Self-citationRudnicka, D., Feldmann, J., Porrot, F., Wietgrefe, S., Guadagnini, S., Prévost, M.-C., Estaquier, J., Haase, A. T., Sol-Foulon, N., & Schwartz, O. (2009) · Journal of Virology · doi:10.1128/jvi.00282-09 · Cited by 229 · see citing works
Mazurov, D., Ilinskaya, A., Heidecker, G., Lloyd, P., & Derse, D. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000788 · Cited by 217 · see citing works
Yu, H. J., Reuter, M. A., & McDonald, D. (2008) · PLoS Pathogens · doi:10.1371/journal.ppat.1000134 · Cited by 193 · see citing works
Kadiu, I., & Gendelman, H. E. (2011) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-011-9298-z · Cited by 100 · see citing works
Martínez-Mármol, R., Giordano-Santini, R., Kaulich, E., Cho, A.-N., Przybyla, M., Riyadh, M. A., Robinson, E., Chew, K. Y., Amor, R., Meunier, F. A., et al. (2023) · Science Advances · doi:10.1126/sciadv.adg2248 · Cited by 94 · see citing works
Liu, S., Hossinger, A., Heumüller, S.-E., Hornberger, A., Buravlova, O., Konstantoulea, K., Müller, S. A., Paulsen, L., Rousseau, F., Schymkowitz, J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25855-2 · Cited by 72 · see citing works
Omsland, M., Pise-Masison, C., Fujikawa, D., Galli, V., Fenizia, C., Parks, R. W., Gjertsen, B. T., Franchini, G., & Andresen, V. (2018) · Scientific Reports · doi:10.1038/s41598-018-29391-w · Cited by 71 · see citing works
HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread
Kalinichenko, S., Komkov, D., & Mazurov, D. (2022) · Viruses · doi:10.3390/v14010152 · Cited by 68 · see citing works
“Subsequently, these authors observed the formation of filopodia bridges (cytonemes) between retrovirus-infected and uninfected cells [105].”
BackgroundTosi, G., Vilella, A., Chhabra, R., Schmeisser, M. J., Boeckers, T. M., Ruozi, B., Vandelli, M. A., Forni, F., Zoli, M., & Grabrucker, A. M. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.01.004 · Cited by 56 · see citing works
Kamel, M., Pavulraj, S., Fauler, B., Mielke, T., & Azab, W. (2020) · iScience · doi:10.1016/j.isci.2020.101615 · Cited by 7 · see citing works
- Authors
- Sherer, N. M., Lehmann, M. J., Jimenez-Soto, L. F., Horensavitz, C., Pypaert, M., & Mothes, W.
- Affiliations
- Yale University (US)
- Heidelberg University (DE)
- Corresponding author
- Mothes, Walther
- Venue
- Nature Cell Biology
- Published
- 2007-02-11
- Volume
- 9
- Issue
- 3
- Pages
- 310-315
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC2628976
- OpenAlex
- W2051695714
- Cited by
- 432
- References
- 26
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 14 · 2023: 8 · 2022: 17 · 2021: 13 · 2020: 25 · 2019: 18 · 2018: 25 · 2017: 15 · 2016: 24 · 2015: 15 · 2014: 31 · 2013: 23 · 2012: 32
- FWCI
- 13.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Searle Scholars Program
- National Institutes of Health
- National Cancer Institute (R01CA098727)
- National Institute of Allergy and Infectious Diseases (R21AI065284)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- retroviruses, cell-to-cell transmission, filopodia, virological synapse, viral envelope glycoprotein, viral receptor, virus transmission, ligand transport, live-cell imaging
- MeSH terms
- Animals, Cell Communication, Cell Line, Chlorocebus aethiops, Endocytosis, Eukaryotic Cells, Humans, Luminescent Proteins, Microscopy, Electron, Scanning, Microscopy, Fluorescence, Mutation, Pseudopodia, Receptors, Virus, Recombinant Fusion Proteins, Retroviridae, Viral Envelope Proteins, HIV-1, CD4 Antigens, COS Cells, Receptors, CXCR4, Avian Proteins, Cell Line, Tumor, TRPV Cation Channels
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
