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.
Poeck
Hendrik
H
III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Bscheider
Michael
M
Gross
Olaf
O
Finger
Katrin
K
Roth
Susanne
S
Rebsamen
Manuele
M
Hannesschläger
Nicole
N
Schlee
Martin
M
Rothenfusser
Simon
S
Barchet
Winfried
W
Kato
Hiroki
H
Akira
Shizuo
S
Inoue
Satoshi
S
Endres
Stefan
S
Peschel
Christian
C
Hartmann
Gunther
G
Hornung
Veit
V
Ruland
Jürgen
J
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
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