Identification of host factors that regulate host susceptibility to hepatitis B virus infection and analysis of mechanisms.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19145
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Tsukuda Senko 国立研究開発法人理化学研究所, 生命医科学研究センター, 研究員 (20710263)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: B型肝炎 / B型肝炎ウイルス / 受容体 / NTCP / 宿主因子

Outline of Final Research Achievements

Recent identification of NTCP as a receptor for hepatitis B virus (HBV) has facilitated the analysis of molecular mechanism of the HBV entry, however, the mechanism has not been fully understood. In this study, we aimed to identify host factors that regulate host susceptibility to HBV infection and analyze mechanisms. We identified host factors that affected on the HBV entry process through a transcriptome analysis of both HBV susceptible and non-susceptible cells. Further analysis revealed that one of the identified factors was involved in the HBV internalization into the cells through the regulation of NTCP localization in the cytosol without affecting NTCP expression. These findings will promote understanding of the mechanism of the HBV entry process after the viral attachment of its receptor.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

B型肝炎ウイルス研究では、汎用的かつ高効率にHBV感染を許容する感染培養細胞系の改善、およびマウスモデルなどのin vivo評価系の樹立が求められている。近年HBV感染受容体としてNTCPが同定され解析が進んだが、HBV侵入過程の詳細な制御機構に関しては未だほとんど不明である。今後さらに詳細な解析が必要であるが、本研究で同定したHBVの細胞内への侵入過程を制御する宿主因子は、HBV感染の動物モデルのあるいは新たな抗HBV薬の標的となり得るため、新たな薬剤開発に寄与できると考えられる。