title: Directional spread of surface-associated retroviruses regulated by differential virus-cell interactions.
abstract: The spread of viral infections involves the directional progression of virus particles from infected cells to uninfected target cells. Prior to entry, the binding of virus particles to specific cell surface receptors can trigger virus surfing, an actin-dependent lateral transport of viruses toward the cell body (M. J. Lehmann et al., J. Cell Biol. 170:317-325, 2005; M. Schelhaas, et al., PLoS Pathog. 4:e1000148, 2008; J. L. Smith, D. S. Lidke, and M. A. Ozbun, Virology 381:16-21, 2008). Here, we have used live-cell imaging to demonstrate that for cells chronically infected with the gammaretrovirus murine leukemia virus in which receptor has been downregulated, a significant portion of completely assembled virus particles are not immediately released into the supernatant but retain long-term association with the cell surface. Retention can be attributed, at least in part, to nonspecific particle attachment to cell surface glycosylaminoglycans. In contrast to virus surfing, viruses retained at the surface of infected cells undergo a lateral motility that is random and actin independent. This diffusive motility can be abruptly halted and converted into inward surfing after treatment with Polybrene, a soluble cation that increases virus-cell adsorption. In the absence of Polybrene, particle diffusion allows for an outward flow of viruses to the infected cell periphery. Peripheral particles are readily captured by and transmitted to neighboring uninfected target cells in a directional fashion. These data demonstrate a surface-based mechanism for the directional spread of viruses regulated by differential virus-cell interactions.
authors.affiliation: Department of Infectious Diseases, King's College London School of Medicine, 2nd floor, Borough Wing, Guy's Hospital, London Bridge, London SE1 9RT, United Kingdom. nathan.sherer@kcl.ac.uk
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Sherer
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Walther
authors.initials: W
authors.lastname: Mothes
mesh_terms: D000818:Animals; D002450:Cell Communication; D002460:Cell Line; D002462:Cell Membrane / Q000821:virology*; D006025:Glycosaminoglycans / Q000502:physiology; D006583:Hexadimethrine Bromide / Q000494:pharmacology; D006801:Humans; D009052:Leukemia Virus, Murine / Q000502:physiology*; D051381:Rats; D014771:Virion / Q000502:physiology; D019065:Virus Assembly
chemical_list: D006025:Glycosaminoglycans; D006583:Hexadimethrine Bromide