• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of the mechanism for maintenance of hepatitis B virus cccDNA

Research Project

Project/Area Number 18K08001
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Ito Masahiko  浜松医科大学, 医学部, 助教 (50385423)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsB型肝炎ウイルス / 潜伏感染 / HBV再活性化 / cccDNA / SET / HBV cccDNA / cccDNA結合タンパク質 / HBV複製 / HBV / 再活性化
Outline of Final Research Achievements

Chronic Hepatitis B virus (HBV) infection is a significant public health problem. Around a million people live with chronic HBV infection in Japan. The viral genome persists in the nuclei of hepatocytes, because covalently closed circular DNA (cccDNA) is stable in nondividing cells. However, the detailed molecular mechanisms underlying formation of cccDNA minichromosome and transcriptional reactivation of the viral cccDNA are poorly understood. From the exploration of the host factors associated with cccDNA, SET were identified. Knockdown or knockout of SET results in enhanced expression of cccDNA and pgRNA. In addition, SET was involved in cccDNA formation from double strand linear DNA via Histone H2AX. In this study, I elucidated that the involvement of SET on the HBV lifecycle and the molecular mechanism of latency and reactivation of HBV. The results obtained in this study lead to development of novel antiviral therapeutic agents or removal of cccDNA from the patients.

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。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (14 results)

All 2021 2020 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (8 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] G ATA2 mediates the negative regulation of the prepro-thyrotropin-releasing hormone gene by liganded T3 receptor β2 in the rat hypothalamic paraventricular nucleus2020

    • Author(s)
      Kuroda Go、Sasaki Shigekazu、Matsushita Akio、Ohba Kenji、Sakai Yuki、Shinkai Shinsuke、Nakamura Hiroko Misawa、Yamagishi Satoru、Sato Kohji、Hirahara Naoko、Oki Yutaka、Ito Masahiko、Suzuki Tetsuro、Suda Takafumi
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 11 Pages: e0242380-e0242380

    • DOI

      10.1371/journal.pone.0242380

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influenza A virus enhances ciliary activity and mucociliary clearance via TLR3 in airway epithelium.2020

    • Author(s)
      Kamiya Y, Fujisawa T, Katsumata M, Yasui H, Suzuki Y, Karayama M, Hozumi H, Furuhashi K, Enomoto N, Nakamura Y, Inui N, Setou M, Ito M, Suzuki T, Ikegami K, Suda T.
    • Journal Title

      Respir Res.

      Volume: 21 Issue: 1 Pages: 282-282

    • DOI

      10.1186/s12931-020-01555-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prevalence and viral loads of polyomaviruses BKPyV, JCPyV, MCPyV, TSPyV and NJPyV and hepatitis viruses HBV, HCV and HEV in HIV-infected patients in China.2020

    • Author(s)
      Zhou X, Nakashima K, Ito M, Zhang X, Sakai S, Feng C, Sun H, Chen H, Li T-C, Suzuki T.
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 17066-17066

    • DOI

      10.1038/s41598-020-74244-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characterization of the self-assembly of New Jersey polyomavirus VP1 into virus-like particles and the virus seroprevalence in Japan2019

    • Author(s)
      Zhou X, Bai H, Kataoka M, Ito M, Muramatsu M, Suzuki T, Li TC.
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 13085-13085

    • DOI

      10.1038/s41598-019-49541-y

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Peroxiredoxin 1, a novel HBx-interacting protein, interacts with exsome component 5 and negatively regulates hepatitis B virus (HBV) propagation through degradation of HBV RNA.2019

    • Author(s)
      Lin Deng, Xiang Gan, Masahiko Ito, Ming Chen, Hussein H. Aly, Chieko Matsui, Takayuki Abe, Koichi Watashi,Takaji Wakita, Tetsuro Suzuki, Toru Okamoto, Yoshiharu Matsuura, Masashi Mizokami, Ikuo Shoji, and Hak Hotta.
    • Journal Title

      J. Virol

      Volume: 93 Issue: 6

    • DOI

      10.1128/jvi.02203-18

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell Type Diversity in Hepatitis B Virus RNA Splicing and Its Regulation2019

    • Author(s)
      Ito Noriomi、Nakashima Kenji、Sun Suofeng、Ito Masahiko、Suzuki Tetsuro
    • Journal Title

      Frontiers in Microbiology

      Volume: 10 Pages: 1-11

    • DOI

      10.3389/fmicb.2019.00207

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 連続定量測定系を基盤としたウイルス侵入、複製過程の時間的動態解析2021

    • Author(s)
      伊藤昌彦, 松田麻未, 鈴木亮介, 鈴木哲朗
    • Organizer
      デザイン生命工学研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Nucleosome assembly proteins SET and SETAP-1 regulate HBV cccDNA formation and pregenomic RNA expression.2019

    • Author(s)
      Masahiko Ito, Tetsuro Suzuki.
    • Organizer
      第67回日本ウイルス学会学術集
    • Related Report
      2019 Research-status Report
  • [Presentation] Analysis of HCV RNA Replication in Living Cells by Chronological and Real-time Monitoring System.2019

    • Author(s)
      Masahiko Ito, Xiaoyu Li, Aoyagi Haruyo, Asako Murayama, Shingo Iwami, Koichi Watashi, Takanobu Kato, Aizaki Hideki, Tetsuro Suzuki.
    • Organizer
      HCV2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Regulation of HBV cccDNA formation and pregenomic RNA expression by SET oncoprotein and its associated protein SETAP-1.2019

    • Author(s)
      Masahiko Ito, Tetsuro Suzuki.
    • Organizer
      International HBV Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Involvement of SET nuclear proto-oncogene in HBV pregenomic RNA expression and cccDNA regulation.2019

    • Author(s)
      Masahiko Ito, Tetsuro Suzuki.
    • Organizer
      7th JAPAN-TAIWAN-KOREA HBV Research Symposium 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Exploration and characterization of host factors associated with reactivation of HBV cccDNA2018

    • Author(s)
      Masahiko Ito, Kenji Nakashima, Tetsuro Suzuki.
    • Organizer
      6th TAIWAN-KOREA-JAPAN HBV Research Symposium 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Exploration and characterization of host factors involved in the metabolism and regulation of HBV cccDNA2018

    • Author(s)
      Masahiko Ito, Tetsuro Suzuki.
    • Organizer
      2018 International HBV Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Involvement of SET nuclear proto-oncogene in the regulation of HBV cccDNA2018

    • Author(s)
      Masahiko Ito, Tetsuro Suzuki.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi