Research for analysis of receptor gene used by hepatitis B virus

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08346
• 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: National Center for Global Health and Medicine
• Principal Investigator: Sugiyama Masaya 国立研究開発法人国立国際医療研究センター, その他部局等, テニュアトラック部長 (20612427)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: B型肝炎ウイルス / 感染 / 侵入 / 受容体

Outline of Final Research Achievements

NTCP has been identified as a receptor for hepatitis B virus entry into hepatocytes. However, NTCP is not the only receptor that regulates the entry process, and it is thought that there are other receptors required for infection. We used single-cell RNA-seq to conduct a comprehensive search for genes characteristic of infection-susceptible hepatocytes, leading to the discovery of the RECK gene. In this study, we analysed the binding between HBV and RECK, the localisation relationship between RECK and NTCP, and the details of the cellular uptake process along the HBV entry process in order to clarify whether RECK is a relevant molecule for infection. The role of the RECK gene in the initial process of HBV infection was confirmed in terms of its binding to HBV and its binding to the NTCP gene. It was observed that HBV infection causes changes in RECK levels.

Free Research Field

感染症学

Academic Significance and Societal Importance of the Research Achievements

HBVに対する治療薬の開発はされてきたが、核酸アナログ製剤に留まっている。それ以外の薬剤では十分な効果が期待できない。新規創薬起点を同定するためには、HBVの感染過程を詳細に理解する必要がある。今回の解析を通して、HBV感染に必要な分子を明らかと出来れば、その過程を阻害する薬剤を開発することにつながる。また、既報の分子も含めて、マウス肝細胞やマウス個体で発現させることで、マウスでの安価なHBV感染モデルの確立へつながり、HBVの創薬研究を発展させることができる。