title: Retroviruses can establish filopodial bridges for efficient cell-to-cell transmission.
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 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.
authors.affiliation: Section of Microbial Pathogenesis, Yale University School of Medicine, 295 Congress Ave, New Haven, CT 06536, USA.
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Sherer
authors.forename: Maik J
authors.initials: MJ
authors.lastname: Lehmann
authors.forename: Luisa F
authors.initials: LF
authors.lastname: Jimenez-Soto
authors.forename: Christina
authors.initials: C
authors.lastname: Horensavitz
authors.forename: Marc
authors.initials: M
authors.lastname: Pypaert
authors.forename: Walther
authors.initials: W
authors.lastname: Mothes
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D019556:COS Cells; D002450:Cell Communication / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004705:Endocytosis / Q000502:physiology; D005057:Eukaryotic Cells / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D009154:Mutation; D011554:Pseudopodia / Q000648:ultrastructure / Q000821:virology*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000502:physiology*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D030161:Avian Proteins; D015704:CD4 Antigens; D008164:Luminescent Proteins; D019718:Receptors, CXCR4; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D050916:TRPV Cation Channels; C088745:Tva receptor; D014759:Viral Envelope Proteins