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DDX19 Inhibits Type I Interferon Production by Disrupting TBK1-IKKε-IRF3 Interactions and Promoting TBK1 and IKKε Degradation.

Cell reports | 2019

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.

Pubmed ID: 30699353 RIS Download

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ATCC (tool)

RRID:SCR_001672

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Anti-Mouse IgG (whole molecule)-Peroxidase antibody produced in goat (antibody)

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Phospho-IRF-3 (Ser396) (4D4G) Rabbit mAb (antibody)

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GAPDH antibody (antibody)

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Anti-DDX19B polyclonal antibody (antibody)

RRID:AB_2679645

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Anti-DDX19A antibody produced in rabbit (antibody)

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IRF-3 (D83B9) Rabbit mAb (antibody)

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