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

• DOI: 10.1126/science.1122411
• Publication Date: 2006-01-19T22:08:37Z
• Authors: Ferran Valderrama; João V. Cordeiro; Sibylle Schleich; Friedrich Frischk...; Michael Way
• Keywords: 0301 basic medicine; 0303 health sciences; Genes, Viral; Pyridines; Recombinant Fusion Proteins; Intracellular Signaling Peptides and Proteins; Protein Serine-Threonine Kinases; Phosphoproteins; Amides; Cell Line; Protein Structure, Tertiary; 3. Good health; Cytoskeletal Proteins; 03 medical and health sciences; Cell Movement; Morphogenesis; Animals; Humans; RNA Interference; Enzyme Inhibitors; RNA, Small Interfering; HeLa Cells; Protein Binding; Signal Transduction

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.