Nck- and N-WASP-dependent actin-based motility is conserved in divergent vertebrate poxviruses.
Vaccinia virus enhances its cell-to-cell spread by stimulating actin polymerization via Src- and Abl-mediated phosphorylation of the highly conserved orthopoxvirus protein A36. The Yatapoxvirus, Yaba-like disease virus (YLDV), also induces actin polymerization, although it lacks an obvious A36 ortholog. We found that the YLDV protein YL126 can functionally replace A36 to promote Nck- and N-WASP-dependent actin polymerization. At least five phosphorylated tyrosines in YL126, rather than a single residue as in A36, are able to recruit Nck to promote actin polymerization. As is the case for A36, YL126-mediated actin tail formation is enhanced by the recruitment of Grb2 via a single phosphorylated tyrosine in YL126. Furthermore, highly divergent YL126 orthologs in Yaba monkey tumor, lumpy skin disease, Shope fibroma, myxoma, and swine and squirrel poxviruses also stimulate Nck- and N-WASP-dependent actin polymerization, suggesting that actin-based motility represents a common mechanism to enhance the cell-to-cell spread of vertebrate poxviruses.
Dodding
Mark P
MP
Cell Motility Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Way
Michael
M
D000199:Actins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D019143:Evolution, Molecular; D006801:Humans; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011213:Poxviridae Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D011485:Protein Binding; D014714:Vertebrates / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000235:genetics / Q000378:metabolism*; D014999:Yaba monkey tumor virus / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C078332:Nck protein; D015513:Oncogene Proteins; D014764:Viral Proteins; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal