HBV‐Pol is crucial for HBV‐mediated inhibition of inflammasome activation and IL‐1β production

BACKGROUND & AIMS: Hepatitis B virus (HBV) infection is the most critical factor underlying liver cirrhosis and hepatocellular carcinoma worldwide. IL-1beta and IL-18, generated by activation of the inflammasome/caspase-1 signaling pathway, play important roles in the control and clearance of HBV. However, the specific relationship between the inflammasome response and IFN-alpha resistance or viral persistence is yet to be established. METHODS: Blood samples of patients and supernatant fractions of HBV cell lines were collected for analysis and the effects on inflammasome activation and IL-1beta production evaluated via enzyme-linked immunosorbent assay (ELISA), western blot, quantitative RT-PCR and immunofluorescence. RESULTS: IL-1beta and IL-18 levels produced in sera of IFN-alpha non-responders were significantly lower than those of responders and normal donors. Additionally, expression of IL-1beta and inflammasome components was decreased in peripheral blood mononuclear cells (PBMC) of non-responders, compared with those of responders. In vitro experiments on HepG2, HepG2.2.15 and HepAD38 cell lines showed that HBV induces a significant decrease in IL-1beta production through inhibiting activation of the NF-kappaB signaling and inflammasome/caspase-1 pathways. And hepatitis B virus polymerase (HBV-Pol) appeared crucial for these inhibitory effects of HBV. CONCLUSION: IL-1beta production is suppressed in HBV carriers and IFN-alpha non-responders. HBV induces a significant decrease in IL-1beta production through inhibiting the NF-kappaB signaling and inflammasome pathways, for which HBV-Pol is a crucial requirement. Trial approval number: 20 173 402.