Schroeder, Martina and Baran, Marcin and Bowie, Andrew G. (2008) Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKε-mediated IRF activation. The EMBO Journal, 27. pp. 2147-2157. ISSN 0261-4189

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Abstract

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 and TBK1 and consequently IFN-β 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-β induction by preventing TBK1/IKKε-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/IKKε, 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/IKKε 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 IKKε. Therefore, this study shows for the first time the involvement of a DEAD box helicase in TBK1/IKKε-mediated IRF activation and Ifnb promoter induction.

Item Type:	Article
Keywords:	DEAD box protein; immune evasion; interferon-b; IRF activation; vaccinia virus;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	12663
Identification Number:	https://doi.org/10.1038/ emboj.2008.143
Depositing User:	Martina Schroeder
Date Deposited:	30 Mar 2020 10:47
Journal or Publication Title:	The EMBO Journal
Publisher:	Wiley
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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