Actin-based motility of vaccinia virus mimics receptor tyrosine kinase signalling

Studies of the actin-based motility of the intracellular pathogens Listeria monocytogenes and Shigella flexneri have provided important insight into t he events occurring at the leading edges of motile cells(1-5). Like the bac teria Listeria and Shigella, vaccinia virus, a relative of the causative ag ent of smallpox, uses actin-based motility to spread between cells(6). In c ontrast to Listeria or Shigella, the actin-based motility of vaccinia is de pendent on an unknown phosphotyrosine protein, but the underlying mechanism remains obscure(7). Here we show that phosphorylation of tyrosine 112 in t he viral protein A36R by Src-family kinases is essential for the actin-base d motility of vaccinia. Tyrosine phosphorylation of A36R results in a direc t interaction with the adaptor protein Nck(8) and the recruitment of the En a/VASP family member N-WASP(9) to the site of actin assembly. We also show that Nck and N-WASP are essential for the actin-based motility of vaccinia virus. We suggest that vaccinia virus spreads by mimicking the signalling p athways that are normally involved in actin polymerization at the plasma me mbrane.