Establishment of HBV-sensitive human hepatocyte lines and analysis of HBV essential factors

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15169
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49060:Virology-related
• Research Institution: Okayama University
• Principal Investigator: Ueda Youki 岡山大学, 医歯薬学総合研究科, 助教 (90756074)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: B型肝炎ウイルス(HBV) / Li23/NTCP細胞 / サブクローニング / A8.15.78.10細胞 / HepG2/NTCP細胞 / cGAS,STING経路 / 薬剤感受性

Outline of Final Research Achievements

Cells derived from the human hepatoma cell line HepG2 and engineered to overexpress NTCP: a receptor for HBV, termed HepG2/NTCP cells, are widely used as the cell-based HBV infection and replication systems for HBV research. We recently found that human hepatoma cell line Li23-derived cells overexpressing NTCP (A8 cells subcloned from Li23 cells) were also sensitive to HBV infection. However, the HBV susceptibility of A8 cells was around 1/100 that of HepG2/NTCP cells. In the present study, we successfully established a Li23/NTCP-derived A8.15.78.10 cell line exhibiting high HBV susceptibility equivalent to that of the HepG2/NTCP cells widely used for HBV research. Using A8.15.78.10 and HepG2/NTCP cells, we demonstrated the necessity of plural HBV assay systems using different types of cells for the objective and impartial evaluation of anti-HBV reagents.

Free Research Field

B型肝炎ウイルス

Academic Significance and Societal Importance of the Research Achievements

これまでのHBVの基礎研究においてはHepG2/NTCP細胞という1種類の細胞株のみを用いた研究が大半である。我々は本研究において、抗HBV剤の正当な評価には異なる細胞株を用いたHBVアッセイ系を使用することが必要であることを示した。複数のHBVアッセイ系を用いた評価がを行うことで、抗HBV活性の評価結果の信頼性が上がり、臨床応用に向けた研究の効率化が期待できる。