title: The role of signalling and the cytoskeleton during Vaccinia Virus egress.
abstract: Viruses are obligate intracellular parasites that are critically dependent on their hosts to replicate and generate new progeny. To achieve this goal, viruses have evolved numerous elegant strategies to subvert and utilise the different cellular machineries and processes of their unwilling hosts. Moreover, they often accomplish this feat with a surprisingly limited number of proteins. Among the different systems of the cell, the cytoskeleton is often one of the first to be hijacked as it provides a convenient transport system for viruses to reach their site of replication with relative ease. At the latter stages of their replication cycle, the cytoskeleton also provides an efficient means for newly assembled viral progeny to reach the plasma membrane and leave the infected cell. In this review we discuss how Vaccinia virus takes advantage of the microtubule and actin cytoskeletons of its host to promote the spread of infection into neighboring cells. In particular, we highlight how analysis of actin-based motility of Vaccinia has provided unprecedented insights into how a phosphotyrosine-based signalling network is assembled and functions to stimulate Arp2/3 complex-dependent actin polymerization. We also suggest that the formin FHOD1 promotes actin-based motility of the virus by capping the fast growing ends of actin filaments rather than directly promoting filament assembly. We have come a long way since 1976, when electron micrographs of vaccinia-infected cells implicated the actin cytoskeleton in promoting viral spread. Nevertheless, there are still many unanswered questions concerning the role of signalling and the host cytoskeleton in promoting viral spread and pathogenesis.
authors: Cell Motility Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London, WC2A 3LY, UK.
authors: Flavia
authors: F
authors: Leite
authors: Cell Motility Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London, WC2A 3LY, UK. Electronic address: michael.way@cancer.org.uk.
authors: Michael
authors: M
authors: Way
mesh_terms: D000818:Animals; D001692:Biological Transport; D003599:Cytoskeleton / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D015398:Signal Transduction; D014616:Vaccinia virus / Q000502:physiology*; D057074:Virus Release
keywords: Actin; Microtubules; Signalling; Transport; Vaccinia virus; Viral spread