Mechanistic analysis of hepatitis B virus internalization focusing on NTCP oligomerization

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K23855
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: National Center for Global Health and Medicine (2021); National Institute of Infectious Diseases (2019-2020)
• Principal Investigator: Fukano Kento 国立研究開発法人国立国際医療研究センター, 臨床研究センター, 産学連携推進部 上級研究員 (80848531)
• Project Period (FY): 2019-08-30 – 2022-03-31
• Keywords: B型肝炎ウイルス / 内在化 / NTCP / 多量体

Outline of Final Research Achievements

Elucidation of molecular mechanism for hepatitis B virus (HBV) infection is required for developing of new prevention and treatment against HBV-related liver diseases. Recently, we reported that oligomerization of bile acid transporter (NTCP), which is an HBV entry receptor, plays a critical role in the HBV internalization pathway. In this study, we identified an amino acid essential for NTCP oligomerization by alanine scanning mutagenesis. Additionally, we revealed that NTCP oligomerization is initiated downstream of the NTCP-EGFR interaction and then triggers HBV internalization. This study provides significant insight into the HBV entry mechanisms.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

HBVの細胞内への内在化機構において、NTCPの多量体形成やEGFRとの相互作用が重要であるとこれまで明らかになっているが、その2つの機構の関連性は不明であった。本研究により、NTCP-EGFR相互作用の下流でNTCPの多量体化が起こると明らかになり、HBV感染機構の一端を解明したと同時に、NTCP多量体化およびHBV内在化の過程が新たな創薬標的となり得ることを示した。