HCV genomic RNA activates the NLRP3 inflammasome in human myeloid cells

• Published in: PloS one 2014-01, Vol.9 (1), p.e84953-e84953
• Main Authors: Chen, Wei, Xu, Yongfen, Li, Hua, Tao, Wanyin, Xiang, Yu, Huang, Bing, Niu, Junqi, Zhong, Jin, Meng, Guangxun
• Format: Article
• Language: English
• Subjects: Activation; Amino acids; Apoptosis; Biology; Carrier Proteins - metabolism; Caspase; Caspase-1; Cell activation; Cell Line; Chen, Wei; Cytokines; DEAD Box Protein 58; DEAD-box RNA Helicases - metabolism; Dendritic cells; Gene silencing; Genes; Genetic engineering; Genome, Viral; Genomes; Health aspects; Hepacivirus - genetics; Hepatitis; Hepatitis C; Hepatitis C - metabolism; Hepatitis C - virology; Hepatitis C virus; Humans; Immunology; Infection; Infections; Inflammasomes; Interleukin 18; Interleukin-1beta - biosynthesis; Laboratories; Macrophages; Macrophages - metabolism; Macrophages - virology; Medical research; Medicine; Monocytes; Monocytes - metabolism; Monocytes - virology; Myeloid cells; Myeloid Cells - metabolism; Myeloid Cells - virology; NLR Family, Pyrin Domain-Containing 3 Protein; Oligomerization; Oligomers; Oxygen; Plasma levels; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Receptors, Immunologic; Ribonucleic acid; RNA; RNA, Viral; Rodents; Tumor necrosis factor-TNF; Virions; Virology; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0084953

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. 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. Our results indicate that HCV RNA activates the NLRP3 inflammasome in a ROS-dependent manner, and RIG-I is not required for this process.