title: Helicase proteins DHX29 and RIG-I cosense cytosolic nucleic acids in the human airway system.
abstract: The recognition of cytoplasmic nucleic acid is critical for innate immune responses against microbial infection and is responsible for autoimmunity induced by dead cells. Here, we report the identification of a unique cytosolic nucleic acid cosensor in human airway epithelial cells and fibroblasts: DEAH (Asp-Glu-Ala-His) box polypeptide 29 (DHX29), a member of the DExD/H (Asp-Glu-x-Asp/His)-box helicase family. Knocking down DHX29 by siRNA attenuated the ability of cells to mount type I IFN and IL-6 in response to cytosolic nucleic acids and various viruses by blocking the activation of interferon regulatory factor 3 and NF-κB-p65. The cytosolic nucleic acid sensing by DHX29 in human epithelial cells and fibroblasts is independent of stimulator of interferon genes but is dependent on retinoic acid-inducible gene 1 (RIG-I) and mitochondrial antiviral signaling protein (MAVS). DHX29 binds directly to nucleic acids and interacts with RIG-I and MAVS through its helicase 1 domain, activating the RIG-I-MAVS-dependent cytosolic nucleic acid response. These results suggest that DHX29 is a cytosolic nucleic acid cosensor that triggers RIG-I/MAVS-dependent signaling pathways. This study will have important implications in drug and vaccine design for control of viral infections and viral-induced pathology in the airway.
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204;
authors.forename: Naoshi
authors.initials: N
authors.lastname: Sugimoto
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204;Department of Clinical Immunology and Rheumatology/Infectious Disease, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; and.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mitoma
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204;
authors.forename: Taeil
authors.initials: T
authors.lastname: Kim
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204;
authors.forename: Shino
authors.initials: S
authors.lastname: Hanabuchi
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204;MedImmune, Gaithersburg, MD 20878 Liuyo@medimmune.com.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
mesh_terms: D003600:Cytosol / Q000378:metabolism*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D018076:DNA, Complementary; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D009696:Nucleic Acids / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D020365:RNA Helicases / Q000378:metabolism*; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic; D020545:Respiratory Mucosa / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D014777:Virus Diseases / Q000276:immunology*; D014780:Viruses / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D009696:Nucleic Acids; D011971:Receptors, Immunologic; C534219:DHX29 protein, human; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases
keywords: airway infection; cytosolic sensor