DEAF1 Is a Pellino1-interacting Protein Required for Interferon Production by Sendai Virus and Double-stranded RNA

Abstract Double-stranded (ds) RNA of viral origin, a ligand for Melanoma Differentiation Associatedgene 5 ( MDA5) and Toll-Like Receptor3 ( TLR3), induces the TANK-Binding Kinase 1(TBK1) -dependent phosphorylation and activation of Interferon Regulatory Factor3 ( IRF3) and the E3 ubiquitin ligasePellino1, which are required for interferon β (IFNβ) gene transcription. Here, we report that Pellino1 interacts with the transcription factor Deformed Epidermal Autoregulatory Factor 1 (DEAF1) The interaction is independent of the E3 ligase activity of Pellino1, but weakened by the phosphorylation of Pellino1. We show that DEAF1 binds to the IFNβ promoter and to IRF3and IRF7, that it is required for the transcription of the IFNβ gene and IFNβ secretion in MEFs infected with Sendai virusor transfected with poly(I:C). DEAF1 is also needed for TLR3-dependent IFNβ production. Taken together, our results identify DEAF1 as a novel component of the signal transduction network by which dsRNA of viral origin stimulates IFNβ production.