title: The NLRP3 inflammasome detects encephalomyocarditis virus and vesicular stomatitis virus infection.
abstract: Inflammasomes are cytosolic protein complexes that regulate caspase-1 activation and the secretion of interleukin-1β (IL-1β) and IL-18. Several different inflammasome complexes have been identified, but the NLRP3 inflammasome is particularly notable because of its central role in diseases of inflammation. Recent work has demonstrated an essential role for the NLRP3 inflammasome in host defense against influenza virus. We show here that two other RNA viruses, encephalomyocarditis virus (EMCV) and vesicular stomatitis virus (VSV), activate the NLRP3 inflammasome in dendritic cells and macrophages through a mechanism requiring viral replication. Inflammasome activation in response to both viruses does not require MDA5 or RIG-I signaling. Despite the ability of the NLRP3 inflammasome to detect EMCV and VSV, wild-type and caspase-1-deficient mice were equally susceptible to infection with both viruses. These findings indicate that the NLRP3 inflammasome may be a common pathway for RNA virus detection, but its precise role in the host response may be variable.
authors.affiliation: Institute for Systems Biology, 1441 34th Avenue N., Seattle, WA 98104, USA.
authors.forename: Jayant V
authors.initials: JV
authors.lastname: Rajan
authors.forename: David
authors.initials: D
authors.lastname: Rodriguez
authors.forename: Edward A
authors.initials: EA
authors.lastname: Miao
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
mesh_terms: D000818:Animals; D018188:Cardiovirus Infections / Q000276:immunology / Q000473:pathology*; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D004686:Encephalomyocarditis virus / Q000276:immunology / Q000472:pathogenicity*; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism; D000072640:Interferon-Induced Helicase, IFIH1; D008264:Macrophages / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018353:Rhabdoviridae Infections / Q000276:immunology / Q000473:pathology*; D018116:Vesiculovirus / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C503356:Ddx58 protein, mouse; C510592:Ifih1 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1