Src Mediates a Switch from Microtubule- to Actin-Based Motility of Vaccinia Virus

• Published in: Science (American Association for the Advancement of Science) Vol. 306; no. 5693; pp. 124 - 129
• Main Authors: Newsome, Timothy P., Scaplehorn, Niki, Way, Michael
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 01.10.2004; The American Association for the Advancement of Science
• Subjects: Actins; Actins - metabolism; Animals; Biological and medical sciences; Cell Line; Cell Membrane - metabolism; Cell Membrane - virology; Cell membranes; Cellular biology; Chickens; Consensus Sequence; Enzyme Activation; Experiments; Fundamental and applied biological sciences. Psychology; HeLa Cells; Humans; Iris; Kinesin - metabolism; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - metabolism; Membranes; Microbiology; Microtubules; Microtubules - metabolism; Phosphorylation; Phosphotyrosine - metabolism; Photoreceptors; Physiological aspects; Plasma; Polymerization; Proteins; Recombinant Fusion Proteins - metabolism; Recruitment; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Retinoids; src-Family Kinases - metabolism; Vaccinia; Vaccinia virus; Vaccinia virus - genetics; Vaccinia virus - metabolism; Vaccinia virus - physiology; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - metabolism; Viral Structural Proteins - metabolism; Virion - metabolism; Virions; Virology; Virus replication; Viruses; Virus; Vaccinia virus; Chordopoxvirinae; Motility; Poxviridae; Orthopoxvirus; Cytoskeleton; Infected cell; Microtubule; Host virus relation
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1101509

The cascade of events that leads to vaccinia-induced actin polymerization requires Src-dependent tyrosine phosphorylation of the viral membrane protein A36R. We found that a localized outside-in signaling cascade induced by the viral membrane protein B5R is required to potently activate Src and induce A36R phosphorylation at the plasma membrane. In addition, Src-mediated phosphorylation of A36R regulated the ability of virus particles to recruit and release conventional kinesin. Thus, Src activity regulates the transition between cytoplasmic microtubule transport and actin-based motility at the plasma membrane.