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

Nat Immunol. 2010 Jan;11(1):63-9. doi: 10.1038/ni.1824. Epub 2009 Nov 15.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • CARD Signaling Adaptor Proteins
  • Caspase 1 / metabolism
  • Cell Line
  • Cells, Cultured
  • DEAD Box Protein 58
  • 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*
  • Inflammation / virology
  • Interferon-Induced Helicase, IFIH1
  • Interleukin-1beta / metabolism*
  • Mice
  • Mice, Knockout
  • Models, Biological
  • RNA Virus Infections / immunology
  • RNA Virus Infections / physiopathology
  • RNA Virus Infections / virology
  • 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


  • Adaptor Proteins, Signal Transducing
  • Bcl2l1 protein, mouse
  • CARD Signaling Adaptor Proteins
  • Card9 protein, mouse
  • Interleukin-1beta
  • bcl-X Protein
  • Caspase 1
  • Ddx58 protein, mouse
  • Ifih1 protein, mouse
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1