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Molecular mechanism of hepatitis B virus DNA integration

Research Project

Project/Area Number 19K07583
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49060:Virology-related
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Muramatsu Masamichi  国立感染症研究所, ウイルス第二部, 部長 (20359813)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsB型肝炎 / B型肝炎ウイルス / hepatitis B virus / viral replication / carcinoma / viral DNA integration / integration / chronic hepatitis / cccDNA / tumorigenesis / ゲノム挿入 / ウイルスDNA / ウイルス発がん / p53 / 肝細胞がん
Outline of Research at the Start

B型肝炎ウイルスの発がん誘発過程では、ウイルスDNAが宿主のゲノムに挿入され、これががんゲノム形成を加速させる。ゲノム挿入は、ウイルス側と宿主側のDNA断端形成、断端修復反応に伴うウイルスDNAの宿主ゲノムへの挿入、挿入DNAの安定化とウイルスDNAの恒常的発現、というプロセスを踏むと想定される。そこで本研究では、培養細胞株モデルを使い各プロセスに関わる因子を分子生物学的に決定する。

Outline of Final Research Achievements

During hepatitis B virus related tumorigenesis, viral DNA integration is a key stone genetic alteration. However, fast convenient detection methods have not been available. Target-capture method have been used for this purpose, however, it requires expensive special probes to fish out viral-host DNA junction. Therefore, in this study, we aim to develop a well accessible detection method for viral DNA integration. Two authentic hepatic cell lines containing HBV viral DNA integration were used as a test samples. It was revealed that our novel approach, which is faster and cheaper than the target-capture method, shows comparable ability to detect viral integration events in the test samples comparing the target-capture method.

Academic Significance and Societal Importance of the Research Achievements

現在、B型肝炎の基礎研究では、ウイルス学的な研究や抗ウイルス剤探索などの研究報告は多い。一方、B型肝炎がどのように発癌を誘導するかについては、王道的テーマではあるものの、この十年大きな進展を見たとは言えない状況である。その一つの原因が、ウイルス発癌の中心的分子機構であるウイルスゲノム挿入現象の解析がなかなか進まないからである。本研究は、ゲノム挿入現象の検出方法の開発研究で、結果、新規手法により、手軽にウイルスゲノム挿入が検出できることがわかった。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (13 results)

All 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Open Access: 6 results) Presentation (2 results) (of which Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] カロリンスカ研究所(スウェーデン)

    • Related Report
      2019 Research-status Report
  • [Journal Article] MafF is an antiviral host factor that suppresses transcription from Hepatitis B Virus core promoter2021

    • Author(s)
      Ibrahim Marwa K.、Abdelhafez Tawfeek H.、Takeuchi Junko S.、Wakae Kosho、Sugiyama Masaya、Tsuge Masataka、Ito Masahiko、Watashi Koichi、El Kassas Mohamed、Kato Takanobu、Murayama Asako、Suzuki Tetsuro、Chayama Kazuaki、Shimotohno Kunitada、Muramatsu Masamichi、Aly Hussein H.、Wakita Takaji
    • Journal Title

      Journal of Virology

      Volume: 「-」 Issue: 15

    • DOI

      10.1128/jvi.00767-21

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NTCP Oligomerization Occurs Downstream of the NTCP-EGFR Interaction during Hepatitis B Virus Internalization2021

    • Author(s)
      Fukano Kento、Oshima Mizuki、Tsukuda Senko、Aizaki Hideki、Ohki Mio、Park Sam-Yong、Wakita Takaji、Wakae Kousho、Watashi Koichi、Muramatsu Masamichi
    • Journal Title

      Journal of Virology

      Volume: 95 Issue: 24 Pages: 1-12

    • DOI

      10.1128/jvi.00938-21

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of novel avian and mammalian deltaviruses provides new insights into deltavirus evolution2021

    • Author(s)
      Iwamoto Masashi、Shibata Yukino、Kawasaki Junna、Kojima Shohei、Li Yung-Tsung、Iwami Shingo、Muramatsu Masamichi、Wu Hui-Lin、Wada Kazuhiro、Tomonaga Keizo、Watashi Koichi、Horie Masayuki
    • Journal Title

      Virus Evolution

      Volume: 7 Issue: 1

    • DOI

      10.1093/ve/veab003

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Extracellular vesicles secreted by HBV-infected cells modulate HBV persistence in hydrodynamic HBV transfection mouse model2020

    • Author(s)
      Kakizaki Masatoshi、Yamamoto Yuichiro、Otsuka Motoyuki、Kitamura Kouichi、Ito Masatoshi、Kawai Hideki Derek、Muramatsu Masamichi、Kagawa Tatehiro、Kotani Ai
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 35 Pages: 12449-12460

    • DOI

      10.1074/jbc.ra120.014317

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MCPIP1 reduces HBV-RNA by targeting its epsilon structure2020

    • Author(s)
      Li Yingfang、Que Lusheng、Fukano Kento、Koura Miki、Kitamura Kouichi、Zheng Xin、Kato Takanobu、Aly Hussein Hassan、Watashi Koichi、Tsukuda Senko、Aizaki Hideki、Watanabe Noriyuki、Sato Yuko、Suzuki Tadaki、Suzuki Hiroshi I.、Hosomichi Kazuyoshi、Kurachi Makoto、Wakae Kousho、Muramatsu Masamichi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 20763-20763

    • DOI

      10.1038/s41598-020-77166-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of Two Critical Neutralizing Epitopes in the Receptor Binding Domain of Hepatitis B Virus preS12020

    • Author(s)
      Yato Keigo、Onodera Taishi、Matsuda Mami、Moriyama Saya、Fujimoto Akira、Watashi Koichi、Aizaki Hideki、Tanaka Tomohisa、Moriishi Kohji、Nishitsuji Hironori、Shimotohno Kunitada、Tamura Koji、Takahashi Yoshimasa、Wakita Takaji、Muramatsu Masamichi、Kato Takanobu、Suzuki Ryosuke
    • Journal Title

      Journal of Virology

      Volume: 95 Issue: 5

    • DOI

      10.1128/jvi.01680-20

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] N‐terminal PreS1 Sequence Regulates Efficient Infection of Cell Culture‐generated Hepatitis B Virus2020

    • Author(s)
      Murayama A、Yamada N、Osaki 、Shiina 、Aly H H、Iwamoto M、Tsukuda S、Watashi K、Matsuda M、Suzuki R、Tanaka T、Moriishi K、Suzuki T、Nishitsuji H、Sugiyama M、Mizokami M、Shimotohno K、Wakita T、Muramatsu M、Liang T J、Kato T
    • Journal Title

      Hepatology

      Volume: 「-」 Issue: 2 Pages: 520-532

    • DOI

      10.1002/hep.31308

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Non-nucleoside hepatitis B virus polymerase inhibitors identified by an in vitro polymerase elongation assay2019

    • Author(s)
      Nakajima Shogo、Watashi Koichi、Fukano Kento、Tsukuda Senko、Wakae Kousho、Aizaki Hideki、Muramatsu Masamichi、Wakita Takaji、Toyoda Tetsuya
    • Journal Title

      Journal of Gastroenterology

      Volume: 55 Issue: 4 Pages: 441-452

    • DOI

      10.1007/s00535-019-01643-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Adenosine deaminase acting on RNA-1 (ADAR1) inhibits hepatitis B virus (HBV) replication by enhancing microRNA-122 processing2019

    • Author(s)
      Liu Guangyan、Ma Xiancai、Wang Zhe、Wakae Kousho、Yuan Yaochang、He Zhangping、Yoshiyama Hironori、Iizasa Hisashi、Zhang Hui、Matsuda Mami、Sugiyama Ryuichi、Yuan Zhiyu、Muramatsu Masamichi、Li Linghua
    • Journal Title

      Journal of Biological Chemistry

      Volume: 294 Issue: 38 Pages: 14043-14054

    • DOI

      10.1074/jbc.ra119.007970

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ウイルス感染で発現誘導される宿主変異原酵素APOBECと病態相関2021

    • Author(s)
      村松正道
    • Organizer
      日本環境変異原ゲノム学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] cccDNA 形成機構を狙った B 型肝炎慢性化阻止の基礎研究2019

    • Author(s)
      村松正道
    • Organizer
      平成30年度宮川庚子記念研究財団 研修会
    • Related Report
      2019 Research-status Report
  • [Remarks] ウイルス二部HP

    • URL

      https://www.niid.go.jp/niid/ja/from-vir2.html

    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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