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Study on DNA damage responses for regulation of intranuclear RNA viruses

Research Project

Project/Area Number 17H04083
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionKyoto University

Principal Investigator

Tomonaga Keizo  京都大学, ウイルス・再生医科学研究所, 教授 (10301920)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2019: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
KeywordsRNAウイルス / 細胞核 / DNA損傷
Outline of Final Research Achievements

The aim of this study was to elucidate the interaction of DNA damage responses with replication of intranuclear replicating RNA viruses, such as Borna disease virus (BoDV). In this study, we found that IFI16, a DNA damage sensor molecule, recognizes nuclear replication of BoDV and triggers host immune responses. We also found that DNA-PK, which is involved in the DNA damage response, is localized at BoDV viral factories and of which activation affect BoDV replication. Furthermore, we showed that ADAR2, a nuclear RNA-editing enzyme that is also shown to be associated with DNA damage responses, contributes to avoidance of the innate immune response and the establishment of persistent infection by introducing A-to-G editing into the genomic RNA of BoDV.

Academic Significance and Societal Importance of the Research Achievements

本研究により、核内で増殖するボルナ病ウイルスが、宿主によりDNA損傷と認識され、細胞のDNA損傷反応を誘導するとともに、ウイルスが宿主のDNA損傷機構を利用して複製や感染を成立させている可能性を見出だした。本研究は、核内複製RNAウイルスが宿主ゲノムの損傷機構と関連することを示唆する初めての成果であり、今後、インフルエンザウイルスなどその他の核内複製RNAウイルスの複製阻害や病原性発現のメカニズムの解明へとつながる成果であると考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (24 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (15 results) (of which Int'l Joint Research: 7 results,  Invited: 3 results) Remarks (1 results)

  • [Int'l Joint Research] University of Freiburg(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Inserm/CNRS, IBS(フランス)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] ADAR2 Is Involved in Self and Nonself Recognition of Borna Disease Virus Genomic RNA in the Nucleus.2020

    • Author(s)
      Yanai M, Kojima S, Sakai M, Komorizono R, Tomonaga K Makino A
    • Journal Title

      Journal of Virology

      Volume: 94 Issue: 6 Pages: 01513-01519

    • DOI

      10.1128/jvi.01513-19

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of a reverse transcription-loop-mediated isothermal amplification assay for the detection of parrot bornavirus 4.2020

    • Author(s)
      Komorizono R, Tomonaga K, Makino A
    • Journal Title

      Journal of Virological Methods

      Volume: 275 Pages: 113749-113749

    • DOI

      10.1016/j.jviromet.2019.113749

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular dynamics of actin affects Borna disease virus replication in the nucleus2019

    • Author(s)
      Hirai Yuya、Domae Eisuke、Yoshikawa Yoshihiro、Okamura Hideyuki、Makino Akiko、Tomonaga Keizo
    • Journal Title

      Virus Research

      Volume: 263 Pages: 179-183

    • DOI

      10.1016/j.virusres.2019.02.004

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Degradation of amyloid _ peptide by neprilysin expressed from Borna disease virus vector.2018

    • Author(s)
      Sakai M, Ueda S, Daito T, Asada-Utsugi M, Komatsu Y, Kinoshita A, Maki T, Kuzuya A, Takahashi R, Makino A, Tomonaga K.
    • Journal Title

      Microbiol Immunol.

      Volume: 62 Issue: 7 Pages: 467-472

    • DOI

      10.1111/1348-0421.12602

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Splicing-Dependent Subcellular Targeting of Borna Disease Virus Nucleoprotein Isoforms.2018

    • Author(s)
      Kojima S, Sato R, Yanai M, Komatsu Y, Horie M, Igarashi M, Tomonaga K.
    • Journal Title

      J Virol

      Volume: 93 Issue: 5

    • DOI

      10.1128/jvi.01621-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Linkage between the leader sequence and leader RNA production in Borna disease virus-infected cells.2017

    • Author(s)
      Honda T, Sofuku K, Kojima S, Yamamoto Y, Ohtaki N, Tomonaga K.
    • Journal Title

      Virology

      Volume: 510 Pages: 104-110

    • DOI

      10.1016/j.virol.2017.07.011

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Ribosomal methyltransferase BUD23-TRMT112 is involved in the host chromosomal attachment of Borna disease virus2020

    • Author(s)
      Garcia BC, Horie M, Kojima S, Tomonaga K
    • Organizer
      The 9th Negative Strand Virus-Japan Symposium
    • Related Report
      2019 Annual Research Report
  • [Presentation] Nucleoprotein and phosphoprotein of Borna disease virus 2 increase the rescue efficiency of recombinant Borna disease virus 1.2019

    • Author(s)
      Kanda T, Horie M, Komatsu Y, Sakai M, Tomonaga K.
    • Organizer
      38th Annual Meeting American Society for Virology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of Borna disease virus genome terminal sequences on viral replication and transcription.2019

    • Author(s)
      Kanda T, Horie M, Komatsu Y, Tomonaga K.
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Pathogenicity of variegated squirrel bornavirus.2019

    • Author(s)
      Makino A, Tanaka C, Tomonaga K
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] BoDV utilizes ADAR2 for evasion of innate immune response.2019

    • Author(s)
      Yanai M, Kojima S, Sakai M, Komorizono R, Makino A, Tomonaga K
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Roles of non-coding RNAs from endogenous bornavirus-like elements in Borna disease virus infection2018

    • Author(s)
      Keizo Tomonaga
    • Organizer
      2nd International Symposium on RNA virus persistence
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Intranuclear persistent infection of bornavirus as an evolutionary strategy determining the survival and fitness Systematic investigation of novel lineages of endogenous bornavirus-like elements in vertebrate genomes. (4/2018

    • Author(s)
      Keizo Tomonaga
    • Organizer
      Virus Dynamics Workshop in Japan
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Alternative splicing unmasks an endoplasmic reticulum targeting signal of Borna disease virus nucleoprotein2018

    • Author(s)
      Shohei Kojima, Ryo Sato, Mako Yanai, Yumiko Komatsu, Manabu Igarashi, Masayuki Horie, Keizo Tomonaga.
    • Organizer
      17th Negative Strand RNA Virus
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Translational regulation of Borna disease virus.2018

    • Author(s)
      Akiko Makino, Yutaro Yamamoto, Yuya Hirai, Keizo Tomonaga.
    • Organizer
      17th Negative Strand RNA Virus
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cleavage of viral glycoprotein is involved in the infection efficiency of non-propagating bornaviral vector.2018

    • Author(s)
      Madoka Sakai, Ryo Komorizono, Yumiko Komatsu, Akiko Makino, Keizo Tomonaga.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] RNAスプライシングはボルナ病ウイルスのヌクレオプロテインの多様な細胞内局在を制御する2018

    • Author(s)
      Shohei Kojima, Ryo Sato, Mako Yanai, Yumiko Komatsu, Manabu Igarashi, Masayuki Horie, Keizo Tomonaga.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A double mutation in polymerase L gene enables adaptation of parrot bornavirus-4 to mammalian cell line.2017

    • Author(s)
      Bea Clarise B. Garcia, Yukiko Sassa, Akiko Makino, and Keizo Tomonaga.
    • Organizer
      36th Annual Meeting of the American Society for Virology.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of possible influences of nuclear actin in forming the viral factories of Borna disease virus and its crosstalk with Cajal bodies.2017

    • Author(s)
      Yuya Hirai, Akiko Makino, Hideyuki Okamura and Keizo Tomonaga.
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ADAR2 plays a key role in the maintenance of the persistent infection of Borna disease virus2017

    • Author(s)
      Mako Yanai, Akiko Makino, Keizo Tomonaga
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Bornavirus infection: a new model of evolution and coexistence of RNA viruses.2017

    • Author(s)
      Keizo Tomonaga
    • Organizer
      The National Symposium on Zoonoses Research 2017.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 京都大学ウイルス・再生医科学研究所RNAウイルス分野

    • URL

      https://t.rnavirus.virus.kyoto-u.ac.jp/

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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