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Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKepsilon-mediated IRF activation.

Viruses are detected by different classes of pattern recognition receptors (PRRs), such as Toll-like receptors and RIG-like helicases. Engagement of PRRs leads to activation of interferon (IFN)-regulatory factor 3 (IRF3) and IRF7 through IKKepsilon and TBK1 and consequently IFN-beta induction. Vaccinia virus (VACV) encodes proteins that manipulate host signalling, sometimes by targeting uncharacterised proteins. Here, we describe a novel VACV protein, K7, which can inhibit PRR-induced IFN-beta induction by preventing TBK1/IKKepsilon-mediated IRF activation. We identified DEAD box protein 3 (DDX3) as a host target of K7. Expression of DDX3 enhanced Ifnb promoter induction by TBK1/IKKepsilon, whereas knockdown of DDX3 inhibited this, and virus- or dsRNA-induced IRF3 activation. Further, dominant-negative DDX3 inhibited virus-, dsRNA- and cytosolic DNA-stimulated Ccl5 promoter induction, which is also TBK1/IKKepsilon dependent. Both K7 binding and enhancement of Ifnb induction mapped to the N-terminus of DDX3. Furthermore, virus infection induced an association between DDX3 and IKKepsilon. Therefore, this study shows for the first time the involvement of a DEAD box helicase in TBK1/IKKepsilon-mediated IRF activation and Ifnb promoter induction.

Pubmed ID: 18636090


  • Schröder M
  • Baran M
  • Bowie AG


The EMBO journal

Publication Data

August 6, 2008

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Cell Line
  • Cell Nucleus
  • Chemokine CCL5
  • Cytoplasm
  • DEAD-box RNA Helicases
  • Humans
  • I-kappa B Kinase
  • Interferon Regulatory Factor-3
  • Interferon Regulatory Factor-7
  • Interferon-beta
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Protein-Serine-Threonine Kinases
  • Receptors, Pattern Recognition
  • Vaccinia virus
  • Viral Proteins