title: Divergent roles of β- and γ-actin isoforms during spread of vaccinia virus.
abstract: Actin is a major component of the cytoskeleton and is present as two isoforms in non-muscle cells: β- and γ-cytoplasmic actin. These isoforms are strikingly conserved, differing by only four N-terminal amino acids. During spread from infected cells, vaccinia virus (VACV) particles induce localized actin nucleation that propel virus to surrounding cells and facilitate cell-to-cell spread of infection. Here we show that virus-tipped actin comets are composed of β- and γ-actin. We employed isoform-specific siRNA knockdown to examine the role of the two isoforms in VACV-induced actin comets. Despite the high level of similarity between the actin isoforms, and their colocalization, VACV-induced actin nucleation was dependent exclusively on β-actin. Knockdown of β-actin led to a reduction in the release of virus from infected cells, a phenotype dependent on virus-induced Arp2/3 complex activity. We suggest that local concentrations of actin isoforms may regulate the activity of cellular actin nucleator complexes.
authors.affiliation: School of Life and Environmental Sciences, The University of Sydney, Australia.
authors.forename: N Bishara
authors.initials: NB
authors.lastname: Marzook
authors.affiliation: Vascular Immunology Unit, Department of Pathology, School of Medical Sciences & Marie Bashir Institute, The University of Sydney, Australia.
authors.forename: Sharissa L
authors.initials: SL
authors.lastname: Latham
authors.affiliation: School of Life and Environmental Sciences, The University of Sydney, Australia.
authors.forename: Helena
authors.initials: H
authors.lastname: Lynn
authors.affiliation: School of Life and Environmental Sciences, The University of Sydney, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Mckenzie
authors.affiliation: Department of Pathology-Immunology, Faculty of Medicine, University of Geneva, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Chaponnier
authors.affiliation: Vascular Immunology Unit, Department of Pathology, School of Medical Sciences & Marie Bashir Institute, The University of Sydney, Australia.
authors.forename: Georges E
authors.initials: GE
authors.lastname: Grau
authors.affiliation: School of Life and Environmental Sciences, The University of Sydney, Australia.
authors.forename: Timothy P
authors.identifier: http://orcid.org/0000-0002-2193-596X
authors.initials: TP
authors.lastname: Newsome
mesh_terms: D000199:Actins / Q000378:metabolism*; D006801:Humans; D020033:Protein Isoforms / Q000378:metabolism*; D014616:Vaccinia virus / Q000254:growth & development* / Q000472:pathogenicity
chemical_list: D000199:Actins; D020033:Protein Isoforms
keywords: actin; transport; virus