RT Journal Article SR Electronic(1) A1 Burdette, Dylan A1 Haskett, Adam A1 Presser, Lance A1 McRae, Steven A1 Iqbal, Jawed A1 Waris, GulamYR 2012 T1 Hepatitis C virus activates interleukin-1β via caspase-1-inflammasome complex JF Journal of General Virology, VO 93 IS 2 SP 235 OP 246 DO https://doi.org/10.1099/vir.0.034033-0 PB Microbiology Society, SN 1465-2099, AB THIS ARTICLE HAS BEEN RETRACTEDInterleukin-1β (IL-1β) is a potent pro-inflammatory cytokine involved in the pathogenesis of HCV, but the sensors and underlying mechanisms that facilitate HCV-induced IL-1β proteolytic activation and secretion remains unclear. In this study, we have identified a signalling pathway leading to IL-1β activation and secretion in response to HCV infection. Previous studies have shown the induction and secretion of IL-1β through the inflammasome complex in macrophages/monocytes. Here, we report for the first time the induction and assembly of the NALP3-inflammasome complex in human hepatoma cells infected with HCV (JFH-1). We demonstrate that activation of IL-1β in HCV-infected cells involves the proteolytic processing of pro-caspase-1 into mature caspase-1 in a multiprotein inflammasome complex. Next, we demonstrate that HCV is sensed by NALP3 protein, which recruits the adaptor protein ASC for the assembly of the inflammasome complex. Using a small interfering RNA approach, we further show that components of the inflammasome complex are involved in the activation of IL-1β in HCV-infected cells. Our study also demonstrates the role of reactive oxygen species in HCV-induced IL-1β secretion. Collectively, these observations provide an insight into the mechanism of IL-1β processing and secretion, which is likely to provide novel strategies for targeting the viral or cellular determinants to arrest the progression of liver disease associated with chronic HCV infection., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.034033-0