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Vaccinia Virus-Induced Cell Motility Requires F11L-Mediated Inhibition of RhoA Signaling
Ferran Valderrama,João V. Cordeiro,Sibylle Schleich,Friedrich Frischknecht,*Michael Way
RhoA signaling plays a critical role in many cellular processes,including cell migration. Here we show that the vaccinia F11Lprotein interacts directly with RhoA, inhibiting its signalingby blocking the interaction with its downstream effectors Rho-associatedkinase (ROCK) and mDia. RNA interferencemediated depletionof F11L during infection resulted in an absence of vaccinia-inducedcell motility and inhibition of viral morphogenesis. Disruptionof the RhoA binding site in F11L, which resembles that of ROCK,led to an identical phenotype. Thus, inhibition of RhoA signalingis required for both vaccinia morphogenesis and virus-inducedcell motility.
Cell Motility Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, WC2A 3PX London, UK.
* Present address: Department of Parasitology, Heidelberg UniversitySchool of Medicine, Im Neuenheimer Feld 324, 69120 Heidelberg,Germany.
To whom correspondence should be addressed. E-mail: michael.way{at}cancer.org.uk
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