title: Measles virus V protein inhibits NLRP3 inflammasome-mediated interleukin-1β secretion.
abstract: Inflammasomes are cytosolic protein complexes that stimulate the activation of caspase-1, which in turn induces the secretion of the inflammatory cytokines Interleukin-1β (IL-1β) and IL-18. Recent studies have indicated that the inflammasome known as the NOD-like-receptor-family, pyrin domain-containing 3 (NLRP3) inflammasome recognizes several RNA viruses, including the influenza and encephalomyocarditis viruses, whereas the retinoic acid-inducible gene I (RIG-I) inflammasome may detect vesicular stomatitis virus. We demonstrate that measles virus (MV) infection induces caspase-1-dependent IL-1β secretion in the human macrophage-like cell line THP-1. Gene knockdown experiments indicated that IL-1β secretion in MV-infected THP-1 cells was mediated by the NLRP3 inflammasome but not the RIG-I inflammasome. MV produces the nonstructural V protein, which has been shown to antagonize host innate immune responses. The recombinant MV lacking the V protein induced more IL-1β than the parental virus. THP-1 cells stably expressing the V protein suppressed NLRP3 inflammasome-mediated IL-1β secretion. Furthermore, coimmunoprecipitation assays revealed that the V protein interacts with NLRP3 through its carboxyl-terminal domain. NLRP3 was located in cytoplasmic granular structures in THP-1 cells stably expressing the V protein, but upon inflammasome activation, NLRP3 was redistributed to the perinuclear region, where it colocalized with the V protein. These results indicate that the V protein of MV suppresses NLRP3 inflammasome-mediated IL-1β secretion by directly or indirectly interacting with NLRP3.
authors: Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
authors: Noritaka
authors: N
authors: Komune
authors: Takeshi
authors: T
authors: Ichinohe
authors: Minako
authors: M
authors: Ito
authors: Yusuke
authors: Y
authors: Yanagi
mesh_terms: D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D002460:Cell Line; D006801:Humans; D057131:Immune Evasion; D058847:Inflammasomes / Q000276:immunology*; D053583:Interleukin-1beta / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000821:virology; D008459:Measles virus / Q000276:immunology* / Q000472:pathogenicity*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D010750:Phosphoproteins; C069181:V protein, measles virus; D014764:Viral Proteins