title: DDX1, DDX21, and DHX36 helicases form a complex with the adaptor molecule TRIF to sense dsRNA in dendritic cells.
abstract: The innate immune system detects viral infection predominantly by sensing viral nucleic acids. We report the identification of a viral sensor, consisting of RNA helicases DDX1, DDX21, and DHX36, and the adaptor molecule TRIF, by isolation and sequencing of poly I:C-binding proteins in myeloid dendritic cells (mDCs). Knockdown of each helicase or TRIF by shRNA blocked the ability of mDCs to mount type I interferon (IFN) and cytokine responses to poly I:C, influenza A virus, and reovirus. Although DDX1 bound poly I:C via its Helicase A domain, DHX36 and DDX21 bound the TIR domain of TRIF via their HA2-DUF and PRK domains, respectively. This sensor was localized within the cytosol, independent of the endosomes. Thus, the DDX1-DDX21-DHX36 complex represents a dsRNA sensor that uses the TRIF pathway to activate type I IFN responses in the cytosol of mDCs.
authors.affiliation: Department of Immunology, Center for Cancer Immunology Research, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Taeil
authors.initials: T
authors.lastname: Kim
authors.forename: Musheng
authors.initials: M
authors.lastname: Bao
authors.forename: Valeria
authors.initials: V
authors.lastname: Facchinetti
authors.forename: Sung Yun
authors.initials: SY
authors.lastname: Jung
authors.forename: Amir Ali
authors.initials: AA
authors.lastname: Ghaffari
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.forename: Genhong
authors.initials: G
authors.lastname: Cheng
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D011485:Protein Binding; D012330:RNA, Double-Stranded / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D053487:DEAD-box RNA Helicases; D012330:RNA, Double-Stranded; C476286:Ticam1 protein, mouse; C541494:DDX1 protein, mouse; C528957:DDX21 protein, mouse; C466989:Dhx36 protein, mouse