Analysis of the mechanism of HBV reactivation mediated by SET protein

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07051
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Ito Masahiko 浜松医科大学, 医学部, 助教 (50385423)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: HBV / B型肝炎ウイルス / 潜伏感染 / HBV再活性化 / cccDNA / SET

Outline of Final Research Achievements

Over one million individuals in Japan are estimated to be carriers of hepatitis B virus (HBV), and reactivation triggered by anticancer drugs and immunosuppressants poses a significant clinical issue. In this study, we identified SET as a novel cccDNA-binding protein and demonstrated that the downregulation of SET expression by specific drugs significantly enhances the levels of cccDNA and pgRNA. Additionally, we showed that SET interacts with histone H2AX, implicating its role in the formation of cccDNA from dslDNA. The results of this research not only contribute to understanding the mechanism by which SET regulates the maintenance of cccDNA but also lay the groundwork for the development of new therapeutic agents aimed at inhibiting cccDNA formation, eliminating latent cccDNA, and preventing HBV reactivation.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

B型肝炎ウイルスのキャリアは、本邦にはおよそ100～120万人(人口1％)、世界にはおよそ4億人いることが知られている。キャリアにおけるHBV活性化の抑制や無症候性キャリアからの感染拡大の防止は急務となっている。本研究により明らかになったSETによるHBV cccDNA形成・維持・再活性化機構に関する知見は、cccDNAの形成阻害、潜伏感染したcccDNAの排除、再活性化の抑制するための薬剤の開発に繋がり、多くの患者を救うための治療法に発展する。