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

Authors
  • Lei, Qingsong1, 2
  • Li, Tianju1, 3
  • Kong, Lingna4
  • Li, Lin5
  • Ding, Xiaolin1
  • Wang, Xiaolin1
  • Zhang, Xiaomei1
  • Qin, Bo1
  • 1 Department of Infectious Diseases, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China. , (China)
  • 2 Department of Oncology Radiotherapy Center, Chongqing University Cancer Hospital, Chongqing, China. , (China)
  • 3 Department of Infectious Diseases, Chongqing Ninth Peoples Hospital, Chongqing, China. , (China)
  • 4 School of Nursing, Chongqing Medical University, Chongqing, China. , (China)
  • 5 Department of hepatic diseases, Chongqing Tranditional Chinese Medicine Hospital, Chongqing, China. , (China)
Type
Published Article
Journal
Liver international : official journal of the International Association for the Study of the Liver
Publication Date
Dec 01, 2019
Volume
39
Issue
12
Pages
2273–2284
Identifiers
DOI: 10.1111/liv.14214
PMID: 31419377
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Hepatitis 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. Blood 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. IL-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. IL-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. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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