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Analysis of chronic active EBV infection by comprehensive genome study

Research Project

Project/Area Number 17H04081
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

Kimura Hiroshi  名古屋大学, 医学系研究科, 教授 (30303621)

Co-Investigator(Kenkyū-buntansha) 奥野 友介  名古屋大学, 医学部附属病院, 病院講師 (00725533)
伊藤 嘉規  名古屋大学, 医学系研究科, 准教授 (20373491)
村田 貴之  藤田医科大学, 医学部, 教授 (30470165)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
KeywordsEpstein-Barrウイルス / 慢性活動性EBV感染症 / 欠失ウイルス / 悪性リンパ腫 / ウイルス / 遺伝子 / EBV / CAEBV / 次世代シーケンサー
Outline of Final Research Achievements

Chronic active EBV infection (CAEBV) is an intractable disease which is characterized by EBV-infected T/natural killer cells and recurrent/persistent infectious mononucleosis-like symptoms. To clarify the neoplastic nature and pathogenesis of CAEBV, we performed comprehensive genetic analysis in patients with CAEBV. The study revealed that somatic driver mutations were found in EBV-infected cells, suggesting a unique role of these mutations in neoplastic proliferation of EBV-infected cells. Interestingly, the EBV genome harbored frequent intragenic deletions that were common in various EBV-associated lymphomas. Our findings highlight a pathogenic link between intragenic EBV deletions and EBV-associated lymphomagenesis.

Academic Significance and Societal Importance of the Research Achievements

慢性活動性Epstein-Barr virus(EBV)感染症は、わが国をはじめとする東アジアに多いT/NK細胞性リンパ増殖性疾患である。本症は予後不良で治療法も確立されていない難治性疾患である上に、発症病理についても未だ不明な点が多い。本研究で得られた知見は、慢性活動性EBV感染症のみならずEBV関連リンパ腫や上咽頭がん・胃がんなどEBV関連上皮系腫瘍に共通する分子機構、さらには他の腫瘍ウイルスの発がんメカニズムを解明につながる可能性があると考えている。

Report

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

    (12 results)

All 2020 2019 2018 2017

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results)

  • [Journal Article] Defective Epstein-Barr virus in chronic active infection and haematological malignancy.2019

    • Author(s)
      Okuno Y, Murata T, Sato Y,Yoshida K, Sawada A, Inoue M, Kawa K, Seto M, Ohshima K, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Nishida T, Kiyoi H, Kato S, Nakamura S, Morishima S, Yoshikawa T, Fujiwara S, Shimizu N, Isobe Y, Noguchi M, Kikuta A, Iwatsuki K, Takahashi Y, Kojima S, Ogawa S, Kimura H.
    • Journal Title

      Nat Microbiol.

      Volume: 4 Issue: 3 Pages: 404-413

    • DOI

      10.1038/s41564-018-0334-0

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] S-Like-Phase Cyclin-Dependent Kinases Stabilize the Epstein-Barr Virus BDLF4 Protein To Temporally Control Late Gene Transcription2019

    • Author(s)
      Sato Yoshitaka、Watanabe Takahiro、Suzuki Chihiro、Abe Yuichi、Masud H. M. Abdullah Al、Inagaki Tomoki、Yoshida Masahiro、Suzuki Takeshi、Goshima Fumi、Adachi Jun、Tomonaga Takeshi、Murata Takayuki、Kimura Hiroshi
    • Journal Title

      Journal of Virology

      Volume: 93 Issue: 8

    • DOI

      10.1128/jvi.01707-18

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antitumor activity of cyclin‐dependent kinase inhibitor alsterpaullone in Epstein‐Barr virus‐associated lymphoproliferative disorders2019

    • Author(s)
      Watanabe Takahiro、Sato Yoshitaka、Masud H. M. Abdullah Al、Takayama Masahiro、Matsuda Hiroki、Hara Yuya、Yanagi Yusuke、Yoshida Masahiro、Goshima Fumi、Murata Takayuki、Kimura Hiroshi
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 1 Pages: 279-287

    • DOI

      10.1111/cas.14241

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The BOLF1 gene is necessary for effective Epstein?Barr viral infectivity2019

    • Author(s)
      Masud H. M. Abdullah Al、Watanabe Takahiro、Sato Yoshitaka、Goshima Fumi、Kimura Hiroshi、Murata Takayuki
    • Journal Title

      Virology

      Volume: 531 Pages: 114-125

    • DOI

      10.1016/j.virol.2019.02.015

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Initial Characterization of the Epstein-Barr Virus BSRF1 Gene Product.2019

    • Author(s)
      Yusuke Yanagi、H. M. bdullah Al Masud、Takahiro Watanabe、Yoshitaka Sato、Fumi Goshima、Hiroshi Kimura、Takayuki Murata
    • Journal Title

      Viruses

      Volume: 21 Issue: 3 Pages: 01707-18

    • DOI

      10.3390/v11030285

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BGLF2 Increases Infectivity of Epstein-Barr virus by Activating AP-1 upon de novo Infection.2018

    • Author(s)
      Konishi N, Narita Y, Hijioka F, Masud HMAA, Sato Y, Kimura H, Murata M.
    • Journal Title

      mSphere

      Volume: 3 Issue: 2

    • DOI

      10.1128/msphere.00138-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gene expression analysis of hypersensitivity to mosquito bite, chronic active EBV infection and NK/T-lymphoma/leukemia2017

    • Author(s)
      Kana Washio, Takashi Oka, Lamia Abdalkader, Michiko Muraoka, Akira Shimada, Megumi Oda, Hiaki Sato, Katsuyoshi Takata, Yoshitoyo Kagami, Norio Shimizu, Seiichi Kato, Hiroshi Kimura, Kazunori Nishizaki, Tadashi Yoshino & Hirokazu Tsukahara
    • Journal Title

      Leukemia & Lymphoma

      Volume: 58 Issue: 11 Pages: 1-12

    • DOI

      10.1080/10428194.2017.1304762

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Chronic Active Epstein-Barr Virus Disease.2017

    • Author(s)
      Kimura H, Cohen JI.
    • Journal Title

      Front Immunol

      Volume: 8 Pages: 1867-1867

    • DOI

      10.3389/fimmu.2017.01867

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Chronic Epstein-Barr virus lymphoproliferative disease2020

    • Author(s)
      Hiroshi Kimura
    • Organizer
      12th T-cell Lymphoma Forum
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Epstein-Barr virus in T-/NK- cell tumorigenesis2019

    • Author(s)
      Hiroshi Kimura
    • Organizer
      APBMT&ICBMT 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Genetics of CAEBV and Related Diseases2019

    • Author(s)
      Hiroshi Kimura
    • Organizer
      7th Conference on Histiocytosis
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 慢性活動性EBV感染症に対する包括的遺伝子解析2017

    • Author(s)
      木村 宏
    • Organizer
      第34回日本生化学会北陸支部大会シンポジウム『ウイルス感染病態研究の新潮流』
    • Related Report
      2017 Annual Research Report
    • Invited

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

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