title: DHX9 pairs with IPS-1 to sense double-stranded RNA in myeloid dendritic cells.
abstract: The innate immune system is equipped with many molecular sensors for microbial DNA/RNA to quickly mount antimicrobial host immune responses. In this paper, we identified DHX9, a DExDc helicase family member, as an important viral dsRNA sensor in myeloid dendritic cells (mDCs). Knockdown of DHX9 expression by small heteroduplex RNA dramatically blocked the ability of mDCs to produce IFN-α/β and proinflammatory cytokines in response to polyinosine-polycytidylic acid, influenza A, and reovirus. DHX9 could specifically bind polyinosine-polycytidylic acid via its double-strand RNA binding motifs. DHX9 interacted with IPS-1 via the HelicC-HA2-DUF and CARD domains of DHX9 and IPS-1, respectively. Knockdown of DHX9 expression in mDCs blocked the activation of NF-κB and IFN regulatory factor 3 by dsRNA. Collectively, these results suggest that DHX9 is an important RNA sensor that is dependent on IPS-1 to sense pathogenic RNA.
authors.affiliation: Department of Immunology, Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Yuan
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.forename: Valeria
authors.initials: V
authors.lastname: Facchinetti
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D057809:HEK293 Cells; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D009980:Influenza A virus / Q000276:immunology; D007370:Interferon Type I / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009692:Nucleic Acid Heteroduplexes / Q000494:pharmacology; D011070:Poly I-C / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D018836:Inflammation Mediators; D007370:Interferon Type I; C505371:MAVS protein, human; D009363:Neoplasm Proteins; D009692:Nucleic Acid Heteroduplexes; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D012367:RNA, Viral; C098487:DHX9 protein, human; D053487:DEAD-box RNA Helicases; D011070:Poly I-C