Vaccinia virus-induced cell motility requires F11L-mediated inhibition of RhoA signaling.
RhoA signaling plays a critical role in many cellular processes, including cell migration. Here we show that the vaccinia F11L protein interacts directly with RhoA, inhibiting its signaling by blocking the interaction with its downstream effectors Rho-associated kinase (ROCK) and mDia. RNA interference-mediated depletion of F11L during infection resulted in an absence of vaccinia-induced cell motility and inhibition of viral morphogenesis. Disruption of the RhoA binding site in F11L, which resembles that of ROCK, led to an identical phenotype. Thus, inhibition of RhoA signaling is required for both vaccinia morphogenesis and virus-induced cell motility.
Valderrama
Ferran
F
Cell Motility Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, WC2A 3PX London, UK.
Cordeiro
João V
JV
Schleich
Sibylle
S
Frischknecht
Friedrich
F
Way
Michael
M
D000577:Amides / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005814:Genes, Viral; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009024:Morphogenesis; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014616:Vaccinia virus / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D000099149:Ezrin
D000577:Amides; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011725:Pyridines; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D000099149:Ezrin; C108830:Y 27632