HBV-Pol is crucial for HBV-mediated inhibition of inflammasome activation and IL-1β production
HBV-Pol is crucial for HBV-mediated inhibition of inflammasome activation and IL-1β production
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DOI：
10.1111/liv.14214
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发表时间：
2019-12-01
影响因子：
6.7
通讯作者：
Qin，Bo
中科院分区：
文献类型：
--
作者：
Lei，Qingsong;Li，Tianju;Qin，Bo
背景与目的B型肝炎病毒（HBV）感染是世界范围内肝硬化和肝细胞癌最重要的致病因素。IL-1β和IL-18由炎症体/caspase-1信号通路激活产生，在HBV的控制和清除中发挥重要作用。然而，炎性小体反应和IFN-α抗性或病毒持久性之间的具体关系尚未建立。方法收集患者的血液样品和HBV细胞系的上清液组分进行分析，并通过酶联免疫吸附测定（ELISA），蛋白质印迹，结果IFN-α无应答者血清中IL-1β和IL-18水平显著低于应答者和正常献血员。此外，与应答者相比，无应答者外周血单核细胞（PBMC）中IL-1β和炎性小体组分的表达降低。在HepG 2、HepG2.2.15和HepAD 38细胞系上的体外实验显示，HBV通过抑制NF-κB信号传导和炎性体/caspase-1通路的活化来诱导IL-1β产生的显著降低。结论IL-1β在HBV携带者和IFN-α无应答者中的产生受到抑制。HBV通过抑制NF-κB信号通路和炎性体通路诱导IL-1β产生显著减少，其中HBV-Pol是关键要求。试验批准号：20 173 402。
Background & AimsHepatitis B virus (HBV) infection is the most critical factor underlying liver cirrhosis and hepatocellular carcinoma worldwide. IL‐1β 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‐α resistance or viral persistence is yet to be established.MethodsBlood samples of patients and supernatant fractions of HBV cell lines were collected for analysis and the effects on inflammasome activation and IL‐1β production evaluated via enzyme‐linked immunosorbent assay (ELISA), western blot, quantitative RT‐PCR and immunofluorescence.ResultsIL‐1β and IL‐18 levels produced in sera of IFN‐α non‐responders were significantly lower than those of responders and normal donors. Additionally, expression of IL‐1β 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‐1β production through inhibiting activation of the NF‐κB signaling and inflammasome/caspase‐1 pathways. And hepatitis B virus polymerase (HBV‐Pol) appeared crucial for these inhibitory effects of HBV.ConclusionIL‐1β production is suppressed in HBV carriers and IFN‐α non‐responders. HBV induces a significant decrease in IL‐1β production through inhibiting the NF‐κB signaling and inflammasome pathways, for which HBV‐Pol is a crucial requirement.Trial approval number:20 173 402.