| First Author | Zhang K | Year | 2019 |
| Journal | Cell Rep | Volume | 26 |
| Issue | 5 | Pages | 1258-1272.e4 |
| PubMed ID | 30699353 | Mgi Jnum | J:289833 |
| Mgi Id | MGI:6431985 | Doi | 10.1016/j.celrep.2019.01.029 |
| Citation | Zhang K, et al. (2019) DDX19 Inhibits Type I Interferon Production by Disrupting TBK1-IKKepsilon-IRF3 Interactions and Promoting TBK1 and IKKepsilon Degradation. Cell Rep 26(5):1258-1272.e4 |
| abstractText | 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-kappab kinase epsilon (IKKepsilon)-mediated phosphorylation of interferon regulatory factor 3 (IRF3) by disrupting the interaction between TBK1 or IKKepsilon and IRF3. Additionally, DDX19 recruited Lamtor2 and then formed the TBK1-IKKepsilon-Lamtor2-DDX19-IRF3 complex to suppress IFN production by promoting TBK1 and IKKepsilon 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. |
