DNA-dependent activator of interferon-regulatory factors inhibits hepatitis B virus replication
- Author:
- No author available
- Journal Title:
- World Journal of Gastroenterology
- Issue:
- 22
- DOI:
- 10.3748/wjg.v1 8.i22.2850
- Key Word:
- DNA-dependent activator of interferon regulatory factor;Antiviral activity;Hepatitis B virus;Nuclear factor-KB;Interferon regulatory factor-3
Abstract： 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.
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