首页|DNA-dependent activator of interferon-regulatory factors inhibits hepatitis B virus replication

DNA-dependent activator of interferon-regulatory factors inhibits hepatitis B virus replication

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AIM:To investigate whether DNA-dependent activator of interferon-regulatory factors (DAI) inhibits hepatitis B virus (HBV) replication and what the mechanism is.METHODS:After the human hepatoma cell line Huh7 was cotransfected with DAI and HBV expressing plasmid,viral protein (HBV surface antigen and HBV e antigen) secretion was detected by enzyme-linked immunosorbent assay,and HBV RNA was analyzed by realtime polymerase chain reaction and Northern blotting,and viral DNA replicative intermediates were examined by Southern blotting.Interferon regulatory factor 3 (IRF3) phosphorylation and nuclear translocation were analyzed via Western blotting and immunofluorescence staining respectively.Nuclear factor-kB (NF-KB) activity induced by DAI was detected by immunofluorescence staining of P65 and dual luciferase reporter assay.Transwell co-culture experiment was performed in order to investigate whether the antiviral effects of DAI were dependent on the secreted cytokines.RESULTS:Viral protein secretion was significantly reduced by 57％ (P ＜ 0.05),and the level of total HBV RNA was reduced by 67％ (P ＜ 0.05).The viral core particle-associated DNA was also dramatically downregulated in DAI-expressing Huh7 cells.Analysis of involved signaling pathways revealed that activation of NF-kB signaling was essential for DAI to elicit antiviral response in Huh7 cells.When the NF-kB signaling pathway was blocked by a NF-KB signaling suppressor (IKBα-SR),the anti-HBV activity of DAI was remarkably abrogated.The inhibitory effect of DAI was independent of IRF3 signaling and secreted cytokines.CONCLUSION:This study demonstrates that DAI can inhibit HBV replication and the inhibitory effect is associated with activation of NF-KB but independent of IRF3 and secreted cytokines.

DNA-dependent activator of interferon regulatory factorAntiviral activityHepatitis B virusNuclear factor-KBInterferon regulatory factor-3

Qi-Ying Chen、Ying-Hui Liu、Jian-Hua Li、Ze-Kun Wang、Jiang-Xia Liu、Zheng-HongYuan

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Key Laboratory of Medical Molecular Virology, Ministry of Education and Ministry of Health, Shanghai Medical College, Fudan University, Shanghai 200032, China

Institutes of Biomedical Sciences,Fudan University, Shanghai 200032, China

Grants of The Chinese State Basic ResearchNational Mega Projects for Infectious Diseases

2009CB5225042008ZX 10203

2012

10.3748/wjg.v1 8.i22.2850

世界胃肠病学杂志(英文版)
太原消化病研治中心

世界胃肠病学杂志(英文版)

SCI
影响因子：1.001
ISSN：1007-9327
年,卷(期)：2012.(22)
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