title: Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production.
abstract: Interleukin 1 beta (IL-1 beta) is a potent proinflammatory factor during viral infection. Its production is tightly controlled by transcription of Il1b dependent on the transcription factor NF-kappaB and subsequent processing of pro-IL-1 beta by an inflammasome. However, the sensors and mechanisms that facilitate RNA virus-induced production of IL-1 beta are not well defined. Here we report a dual role for the RNA helicase RIG-I in RNA virus-induced proinflammatory responses. Whereas RIG-I-mediated activation of NF-kappaB required the signaling adaptor MAVS and a complex of the adaptors CARD9 and Bcl-10, RIG-I also bound to the adaptor ASC to trigger caspase-1-dependent inflammasome activation by a mechanism independent of MAVS, CARD9 and the Nod-like receptor protein NLRP3. Our results identify the CARD9-Bcl-10 module as an essential component of the RIG-I-dependent proinflammatory response and establish RIG-I as a sensor able to activate the inflammasome in response to certain RNA viruses.
authors.affiliation: III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Poeck
authors.forename: Michael
authors.initials: M
authors.lastname: Bscheider
authors.forename: Olaf
authors.initials: O
authors.lastname: Gross
authors.forename: Katrin
authors.initials: K
authors.lastname: Finger
authors.forename: Susanne
authors.initials: S
authors.lastname: Roth
authors.forename: Manuele
authors.initials: M
authors.lastname: Rebsamen
authors.forename: Nicole
authors.initials: N
authors.lastname: Hannesschläger
authors.forename: Martin
authors.initials: M
authors.lastname: Schlee
authors.forename: Simon
authors.initials: S
authors.lastname: Rothenfusser
authors.forename: Winfried
authors.initials: W
authors.lastname: Barchet
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kato
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.forename: Stefan
authors.initials: S
authors.lastname: Endres
authors.forename: Christian
authors.initials: C
authors.lastname: Peschel
authors.forename: Gunther
authors.initials: G
authors.lastname: Hartmann
authors.forename: Veit
authors.initials: V
authors.lastname: Hornung
authors.forename: Jürgen
authors.initials: J
authors.lastname: Ruland
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D053468:CARD Signaling Adaptor Proteins; D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D004686:Encephalomyocarditis virus / Q000276:immunology / Q000502:physiology; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D054884:Host-Pathogen Interactions; D006801:Humans; D015151:Immunoblotting; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D000072640:Interferon-Induced Helicase, IFIH1; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D012327:RNA Virus Infections / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D012328:RNA Viruses / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology / Q000502:physiology; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C494812:Bcl2l1 protein, mouse; D053468:CARD Signaling Adaptor Proteins; C513280:Card9 protein, mouse; D053583:Interleukin-1beta; D051020:bcl-X Protein; D020170:Caspase 1; C503356:Ddx58 protein, mouse; C510592:Ifih1 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1