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Science 311 (5759): 377-381

Copyright © 2006 by the American Association for the Advancement of Science

Vaccinia Virus-Induced Cell Motility Requires F11L-Mediated Inhibition of RhoA Signaling

Ferran Valderrama, João V. Cordeiro, Sibylle Schleich, Friedrich Frischknecht,* Michael Way{dagger}

Abstract: 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.

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 University School of Medicine, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.

{dagger} To whom correspondence should be addressed. E-mail: michael.way{at}cancer.org.uk


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