title: Repulsion of superinfecting virions: a mechanism for rapid virus spread.
abstract: Viruses are thought to spread across susceptible cells through an iterative process of infection, replication, and release, so that the rate of spread is limited by replication kinetics. Here, we show that vaccinia virus spreads across one cell every 75 minutes, fourfold faster than its replication cycle would permit. To explain this phenomenon, we found that newly infected cells express two surface proteins that mark cells as infected and, via exploitation of cellular machinery, induce the repulsion of superinfecting virions away toward uninfected cells. Mechanistically, early expression of proteins A33 and A36 was critical for virion repulsion and rapid spread, and cells expressing these proteins repelled exogenous virions rapidly. Additional spreading mechanisms may exist for other viruses that also spread faster than predicted by replication kinetics.
authors.affiliation: Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
authors.forename: Virginie
authors.initials: V
authors.lastname: Doceul
authors.affiliation: Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Hollinshead
authors.affiliation: Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
authors.forename: Lonneke
authors.initials: L
authors.lastname: van der Linden
authors.affiliation: Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Smith
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D005814:Genes, Viral; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D014616:Vaccinia virus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D010948:Viral Plaque Assay; D015678:Viral Structural Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000502:physiology; D057074:Virus Release; D014779:Virus Replication
chemical_list: C446940:A33R protein, Vaccinia virus; C400287:A36R protein, Vaccinia virus; D000199:Actins; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; D015678:Viral Structural Proteins