Article: article from journal or magazin.
Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production.
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.
Adaptor Proteins, Signal Transducing/genetics, Adaptor Proteins, Signal Transducing/metabolism, Animals, Caspase 1/metabolism, Cell Line, Cells, Cultured, DEAD-box RNA Helicases/genetics, DEAD-box RNA Helicases/metabolism, Encephalomyocarditis virus/immunology, Encephalomyocarditis virus/physiology, Enzyme Activation, Enzyme-Linked Immunosorbent Assay, Host-Pathogen Interactions, Humans, Immunoblotting, Inflammation/immunology, Inflammation/physiopathology, Interleukin-1beta/metabolism, Mice, Mice, Knockout, Models, Biological, RNA Virus Infections/immunology, RNA Virus Infections/physiopathology, RNA Viruses/immunology, RNA Viruses/physiology, Signal Transduction, Vesicular stomatitis Indiana virus/immunology, Vesicular stomatitis Indiana virus/physiology, bcl-X Protein/genetics, bcl-X Protein/metabolism
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