Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1β production

• DOI: 10.1038/ni.1824
• Publication Date: 2009-11-15T19:20:10Z
• Authors: Hendrik Poeck; Michael Bscheider; Olaf Gross; Katrin Finger; Susanne Roth; Manuele Rebsamen; Nicole Hannesschl...; Martin Schlee; Simon Rothenfusser; Winfried Barchet; Hiroki Kato; Shizuo Akira; Satoshi Inoue; Stefan Endres; Christian Peschel; Gunther Hartmann; Veit Hornung; Jürgen Ruland
• Keywords: Inflammation; Mice, Knockout; 0301 basic medicine; Interferon-Induced Helicase, IFIH1; Caspase 1; Immunoblotting; Interleukin-1beta; Enzyme-Linked Immunosorbent Assay; Models, Biological; Cell Line; 3. Good health; CARD Signaling Adaptor Proteins; DEAD-box RNA Helicases; Enzyme Activation; Mice; 03 medical and health sciences; Host-Pathogen Interactions; Animals; DEAD Box Protein 58; Humans; Encephalomyocarditis virus; Cells, Cultured; Adaptor Proteins, Signal Transducing

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.