Analyses of antiviral mechanisms by interferon treatment on hepatitis B virus replication

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07973
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Hiroshima University
• Principal Investigator: TSUGE MASATAKA 広島大学, 自然科学研究支援開発センター, 助教 (50448263)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: B型肝炎 / インターフェロン / 抗ウイルス効果

Outline of Final Research Achievements

I compared the induction of interferon stimulated genes (ISGs) between by PEG-IFNα2a and PEG-IFNβ using hepatoma cell line. When I treated hepatoma cells with PEG-IFNs, I found that 34% of ISGs were more strongly induced by PEG-IFNβ treatment rather than by PEG-IFNα2a treatment. Additionally, I also found that the induction rates of several ISGs were enhanced or reduced by HBV expression.
To identify the molecular target for the improvement of antiviral effects by interferon treatment, I focused on gene A and further analyses were performed. I found that gene A is upregulated by HBV infection using human hepatocyte chimeric mouse model and also found that the expression of gene A could be regulated by HBx protein using in vitro HBV expression model. Furthermore, I clarified that host immune response might be suppressed by gene A upregulation.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

本研究成果から、同定した遺伝子は、B型肝炎ウイルス感染に伴い活性化する生体内の免疫応答やインターフェロンにより活性化された免疫応答を回避し、B型肝炎ウイルスの持続感染に関与しているものと考えられる。現在、同遺伝子の発現制御を行い、インターフェロンによる抗ウイルス効果を制御できる化合物を探索中であり、化合物を同定できれば、B型肝炎ウイルス持続感染者に対する抗ウイルス療法の新たなオプションとなりうると考えられる。