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miR146a impairs the IFN ‐induced anti‐ HBV immune response by downregulating STAT 1 in hepatocytes
Author(s) -
Hou Zhao H.,
Han Qiu J.,
Zhang Cai,
Tian Zhi G.,
Zhang Jian
Publication year - 2014
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12244
Subject(s) - interferon , biology , hepatitis b virus , virology , gene silencing , immune system , cancer research , immunology , virus , gene , biochemistry
Background & Aims Previous studies have shown that hepatitis B virus ( HBV ) interferes with host antiviral immunity via multiple pathways. In clinical practice, interferon resistance is a serious issue for treatment of HBV infection. Now, mi RNA s have been reported to be widely involved in antiviral immunity and have become a novel tool to study virus–host interaction. We question whether mi RNA s play a role in HBV ‐induced interferon resistance in hepatocytes. Methods MiRNAs levels in HepG2 and HepG2.2.15 cells were compared by qRT ‐PCR. The effects of miR146a on HBV infection were characterized by interference miR146a level, followed by the quantification of HBV mRNA , DNA and antigens. We employed qRT ‐PCR and western blot to study the effects of miR146a on the IFN‐α signalling pathway. The miR146a promoter activity was validated by a luciferase reporter assay. Results HBV infection impaired IFN ‐α signalling pathway in hepatocytes. MiR146a was upregulated in HBV + HepG2.2.15 cells, and the transcriptional activity of miR146a in HepG2.2.15 cells was increased compared with HepG2 cells. HBV infection, especially the introduction of HB x, induced miR146a expression in vitro . Moreover, miR146a attenuated the production of type I interferon‐induced antiviral factors. Low STAT 1 levels were noticed in HBV + HCC cells, and the luciferase reporter assay showed that STAT 1 was post‐transcriptionally downregulated by miR146a. Furthermore, the silencing of miR146a by antisense inhibitors enhanced IFN ‐α‐mediated anti‐ HBV efficiency. Conclusions Our findings demonstrate that HBV infection promotes miR146a transcription, which represses STAT 1 and results in interferon resistance. These observations reveal a novel role for miR146a in HBV immunopathogenesis, and provide a potential target for the therapeutic recovery of IFN ‐α‐induced anti‐ HBV effects.