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Functional role of pregenomic RNA splicing in Hepatitis B virus replication

Research Project

Project/Area Number 16K19137
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Virology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Nakashima Kenji  浜松医科大学, 医学部, 助教 (50633806)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsB型肝炎ウイルス / スプライシング / ヌクレオカプシド
Outline of Final Research Achievements

The splicing of hepatitis B virus (HBV) pregenomic (pg)RNA is common event in HBV life cycle. However, the functional role of pgRNA splicing remains a critical unanswered question. In this study, we found that HBc lacking its C-terminal Cys (HBc-delC) is translated from the major type of the spliced RNA (Sp1) and that HBc-delC is involved in HBV nucleocapsid. Futhermore, it is hihgly likely that co-existence of two types of HBc proteins produced from unspliced pgRNA and from spliced pgRNA (Sp1) is important for HBV infectivity.

Academic Significance and Societal Importance of the Research Achievements

スプライシングを受けたHBV pgRNAから、これまでに知られていなかったウイルスタンパク質が作られていることが明らかとなった。さらに、この新規タンパク質がウイルス粒子に含まれており、さらには感染性に関わっていることを示唆する結果が得られた。この結果はこれまで考えられていたB型肝炎ウイルスの構造に関する理解を覆す可能性があることを示している。またHBV pgRNAのスプライシングを標的とした新たな治療法の開発が可能となることが期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (12 results)

All 2019 2018 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 2 results)

  • [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 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Critical role of CREBH-mediated induction of transforming growth factor β2 by hepatitis C virus infection in fibrogenic responses in hepatic stellate cells2017

    • Author(s)
      Chida Takeshi、Ito Masahiko、Nakashima Kenji、Kanegae Yumi、Aoshima Takuya、Takabayashi Shuji、Kawata Kazuhito、Nakagawa Yoshimi、Yamamoto Masahiro、Shimano Hitoshi、Matsuura Tomokazu、Kobayashi Yoshimasa、Suda Takafumi、Suzuki Tetsuro
    • Journal Title

      Hepatology

      Volume: 66 Issue: 5 Pages: 1430-1443

    • DOI

      10.1002/hep.29319

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Involvement of PUF60 in Transcriptional and Post-transcriptional Regulation of Hepatitis B Virus Pregenomic RNA Expression2017

    • Author(s)
      Sun Suofeng、Nakashima Kenji、Ito Masahiko、Li Yuan、Chida Takeshi、Takahashi Hirotaka、Watashi Koichi、Sawasaki Tatsuya、Wakita Takaji、Suzuki Tetsuro
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 12874-12874

    • DOI

      10.1038/s41598-017-12497-y

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of hepatoma-derived, bidirectional oval-like cells as a model to study host interactions with hepatitis C virus during differentiation2017

    • Author(s)
      Ito Masahiko、Sun Suofeng、Fukuhara Takasuke、Suzuki Ryosuke、Tamai Miho、Yamauchi Toyohiko、Nakashima Kenji、Tagawa Yoh-ichi、Okazaki Shigetoshi、Matsuura Yoshiharu、Wakita Takaji、Suzuki Tetsuro
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 33 Pages: 53899-53915

    • DOI

      10.18632/oncotarget.19108

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] LUC7L3/CROP inhibits replication of hepatitis B virus via suppressing enhancer II/basal core promoter activity.2016

    • Author(s)
      Li Y, Ito M, Sun S, Chida T, Nakashima K, Suzuki T.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 36741-36741

    • DOI

      10.1038/srep36741

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Regulation of HBV pregenomic RNA splicing2018

    • Author(s)
      Kenji Nakashima, Noriomi Ito, Masahiko Ito, Tetsuro Suzuki
    • Organizer
      The 66th Annual Meeting of the Japanese Society for Virology
    • Related Report
      2018 Annual Research Report
  • [Presentation] Identification of positive regulators of HBV pregenomic RNA expression that bind to the post-transcriptional element of the viral RNA2017

    • Author(s)
      Kenji Nakashima, Masahiko Ito, Suofeng Sun, Tetsuro Suzuki
    • Organizer
      The 65th Annual Meeting of the Japanese Society for Virology
    • Related Report
      2017 Research-status Report
  • [Presentation] Critical role of CREBH-dependent transcriptional activation of TGF-beta2 by HCV infection in profibrogenic responses in hepatic stellate cells2017

    • Author(s)
      Masahiko Ito, Takeshi Chida, Kenji Nakashima, Yumi Kanegae, Kazuhito Kawata, Yoshimasa Kobayashi, Takafumi Suda, Tetsuro Suzuki
    • Organizer
      The 65th Annual Meeting of the Japanese Society for Virology
    • Related Report
      2017 Research-status Report
  • [Presentation] Potential role of spliced RNA-encoded HBc lacking its C-terminal cysteine2017

    • Author(s)
      Kenji Nakashima, Suofeng Sun, Masahiko Ito, Tetsuro Suzuki
    • Organizer
      2017 International HBV Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Involvement of the spliced RNA-encoded HBc lacking its C-terminal cysteine in the viral capsid assembly2016

    • Author(s)
      Nakashima K, Ito M, Suzuki T.
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Research-status Report
  • [Presentation] PUF60: a versatile regulator of hepatitis B virus replication2016

    • Author(s)
      Sun S, Nakashima K, Ito M, Suzuki T.
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Research-status Report
  • [Presentation] Involvement of the spliced RNA-encoded HBc lacking its C-terminal cysteine in the viral capsid assembly2016

    • Author(s)
      Nakashima K, Ito M, Suzuki T.
    • Organizer
      2016 International HBV meeting
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2016-09-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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