J Gen Virol. 2012 Feb;93(Pt 2):235-46. Epub 2011 Oct 12.

Hepatitis C virus activates interleukin-1beta via caspase-1-inflammasome complex.External

Burdette, D., Haskett, A., Presser, L., McRae, S., Iqbal, J., Waris, G.,
--- - Department of Microbiology and Immunology, H. M. Bligh Cancer Research Laboratories, Rosalind Franklin University of Medicine and Science, Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, USA.
Interleukin-1beta (IL-1beta) is a potent pro-inflammatory cytokine involved in the pathogenesis of HCV, but the sensors and underlying mechanisms that facilitate HCV-induced IL-1beta proteolytic activation and secretion remains unclear. In this study, we have identified a signalling pathway leading to IL-1beta activation and secretion in response to HCV infection. Previous studies have shown the induction and secretion of IL-1beta 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-1beta 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-1beta in HCV-infected cells. Our study also demonstrates the role of reactive oxygen species in HCV-induced IL-1beta secretion. Collectively, these observations provide an insight into the mechanism of IL-1beta 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.
PMID: 21994322External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
PYD ASC Link NLRP3 Co-immunoprecipitation HuH-7.5 21994322
(Link: click this icon to show interactions only between the two corresponding DDs)