DDX19 Inhibits Type I Interferon Production by Disrupting TBK1-IKKε-IRF3 Interactions and Promoting TBK1 and IKKε Degradation
In: Cell Reports, Jg. 26 (2019), Heft 5, S. 1258-1272.e4
Online
academicJournal
Zugriff:
Summary: DExD/H-box helicase members are key receptors for recognizing viral nucleic acids, and they regulate retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)-mediated type I interferon (IFN) production. Here, we report that the DExD/H-box helicase family member DExD/H-box RNA helicase 19 (DDX19) is a negative regulator of type I IFN production. Ectopic expression of DDX19 suppressed poly(I:C) (polyinosinic-polycytidylic acid)- and Sendai-virus-induced type I IFN production, whereas knockdown of DDX19 expression enhanced type I IFN production. Mechanistically, DDX19 inhibited TANK-binds kinase 1 (TBK1)- and inhibitor-κb kinase ε (IKKε)-mediated phosphorylation of interferon regulatory factor 3 (IRF3) by disrupting the interaction between TBK1 or IKKε and IRF3. Additionally, DDX19 recruited Lamtor2 and then formed the TBK1-IKKε-Lamtor2-DDX19-IRF3 complex to suppress IFN production by promoting TBK1 and IKKε degradation. We generated Ddx19 knockout mice using transcription activator-like effector nucleases (TALENs) and found that Ddx19 deficiency in vivo augmented type I IFN production, resulting in suppression of encephalomyocarditis virus replication. These data show that DDX19 is an important negative regulator of RLR-mediated type I IFN production. : DExD/H-box helicase members are key receptors for recognizing viral nucleic acids and participate in regulating RLR-mediated type I IFN production. Zhang et al. show that DDX19 acts as a critical negative regulator of type I IFN production by disrupting TBK1-IKKε-IRF3 complex formation and recruiting Lamtor2 to degrade TBK1 and IKKε. Keywords: DDX19, IRF3, IKKε, Lamtor2, negative regulatory, type I IFN, TBK1
Titel: |
DDX19 Inhibits Type I Interferon Production by Disrupting TBK1-IKKε-IRF3 Interactions and Promoting TBK1 and IKKε Degradation
|
---|---|
Autor/in / Beteiligte Person: | Zhang, Kunli ; Zhang, Yuanfeng ; Xue, Juan ; Meng, Qingwen ; Liu, Hongyang ; Bi, Caihong ; Li, Changyao ; Hu, Liang ; Yu, Huibin ; Xiong, Tao ; Yang, Yuying ; Cui, Shangjin ; Bu, Zhigao ; He, Xijun ; Li, Jiangnan ; Huang, Li ; Weng, Changjiang |
Link: | |
Zeitschrift: | Cell Reports, Jg. 26 (2019), Heft 5, S. 1258-1272.e4 |
Veröffentlichung: | Elsevier, 2019 |
Medientyp: | academicJournal |
ISSN: | 2211-1247 (print) |
DOI: | 10.1016/j.celrep.2019.01.029 |
Schlagwort: |
|
Sonstiges: |
|