title: HCV genomic RNA activates the NLRP3 inflammasome in human myeloid cells.
abstract: BACKGROUND
  Elevated plasma levels of IL-1β and IL-18 from patients with hepatitis C virus (HCV) infection indicate a possible activation of inflammasome by HCV.
  
  
  RESULTS
  To demonstrate whether HCV infection activates the inflammasome, we investigated inflammasome activation from HCV infected hepatic Huh7 cells, or monocytic cells and THP-1 derived macrophages challenged with HCV virions, but no any inflammasome activation was detected in these cells. However, when we transfected HCV genomic RNA into monocytes or macrophages, IL-1β was secreted in a dose-dependent manner. We also detected ASC oligomerization and caspase-1 cleavage in HCV RNA transfected macrophages. Using shRNA-mediated gene silencing or specific inhibitors, we found that HCV RNA-induced IL-1β secretion was dependent on the presence of inflammasome components such as NLRP3, ASC and caspase-1. Furthermore, we also found that RIG-I was dispensable for HCV RNA-induced NLRP3 inflammasome activation, while reactive oxygen species (ROS) production was required.
  
  
  CONCLUSIONS
  Our results indicate that HCV RNA activates the NLRP3 inflammasome in a ROS-dependent manner, and RIG-I is not required for this process.
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yongfen
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Wanyin
authors.initials: W
authors.lastname: Tao
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Hepatology, The First Hospital of Jilin University, Changchun, China.
authors.forename: Junqi
authors.initials: J
authors.lastname: Niu
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Guangxun
authors.initials: G
authors.lastname: Meng
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000378:metabolism* / Q000821:virology; D006801:Humans; D058847:Inflammasomes; D053583:Interleukin-1beta / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D009000:Monocytes / Q000378:metabolism / Q000821:virology; D022423:Myeloid Cells / Q000378:metabolism* / Q000821:virology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012367:RNA, Viral; D017382:Reactive Oxygen Species / Q000378:metabolism; D011971:Receptors, Immunologic
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D012367:RNA, Viral; D017382:Reactive Oxygen Species; D011971:Receptors, Immunologic; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases