Article

  • The EMBO Journal (2008) 27, 2147 - 2157
  • doi:10.1038/emboj.2008.143

Published online: 17 July 2008

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

Martina Schröder1, Marcin Baran1 and Andrew G Bowie1

  1. Viral Immune Evasion Group, School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland

Correspondence to:

Andrew G Bowie, Viral Immune Evasion Group, School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland. Tel.: +353 1 8962435; Fax: +353 1 6772400; E-mail: agbowie@tcd.ie

Received 21 February 2008; Accepted 2 July 2008


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 IKKalt epsilon 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/IKKalt epsilon-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/IKKalt epsilon, 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/IKKalt epsilon 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 IKKalt epsilon. Therefore, this study shows for the first time the involvement of a DEAD box helicase in TBK1/IKKalt epsilon-mediated IRF activation and Ifnb promoter induction.

  • Keywords:

    • DEAD box protein,
    • immune evasion,
    • interferon-beta,
    • IRF activation,
    • vaccinia virus