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Cooperative epithelial cell tumorigenesis by APOBEC3s expressed in the nucleus and cytoplasm induced by EBV infection

Research Project

Project/Area Number 18K15168
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49060:Virology-related
Research InstitutionShimane University

Principal Investigator

Kanehiro Yuichi  島根大学, 学術研究院医学・看護学系, 助教 (60609197)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsEBウイルス / APOBEC3 / ミトコンドリア / EBV / 上皮性腫瘍
Outline of Final Research Achievements

We studied the role of the nuclear- and cytoplasm-localized DNA editing enzyme APOBEC3 in the tumorigenesis of EBV-infected epithelial cells.Infection experiments using recombinant EBV-eGFP revealed that EBV infection induces the expression of cytoplasm-localized APOBEC3C via type I IFNs and that mitochondria are injured by mutations in mtDNA by APOBEC3C.Since the nuclear-localized APOBEC3A is also induced by type I IFNs, we hypothesized that cytoplasm-localized and nuclear-localized APOBEC3 induced by EBV infection would introduce mutations into the host and mitochondrial genomes in a coordinated manner, leading to cell tumorigenesis.

Academic Significance and Societal Importance of the Research Achievements

EBウイルス陽性上皮細胞性腫瘍は、単一のウイルス感染細胞が腫瘍化したものである。EBV感染がAPOBEC3を介して宿主ゲノムやミトコンドリアゲノムに変異を導入し、細胞を腫瘍化に導くとすれば、APOBEC3は発がんのリスク因子となりうる。従って、EBV感染が誘導するAPOBEC3による腫瘍化機構を明らかにすれば、EBV感染で発生する上皮細胞性腫瘍の予防法が開発できる。また宿主ゲノムやミトコンドリアゲノムへの変異は、多くのウイルス感染に共通の現象である可能性が高く、本研究は多くのウイルス感染による腫瘍の発生にAPOBEC3が関わっている可能性を示すことになる。

Report

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

    (20 results)

All 2020 2019 2018

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (13 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] ヘルペスウイルス感染症の特徴2020

    • Author(s)
      金廣優一、飯笹久、康宇、丁丹、上野詩織、飯田慶治、吉山裕規
    • Journal Title

      島根医学

      Volume: 39 Pages: 113-120

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Role of Viral and Host microRNAs in Immune Regulation of Epstein-Barr Virus-Associated Diseases.2020

    • Author(s)
      Iizasa H, Kim H, Kartika AV, Kanehiro Y, Yoshiyama H.
    • Journal Title

      Front Immunol.

      Volume: 11 Pages: 367-367

    • DOI

      10.3389/fimmu.2020.00367

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epstein-Barr Virus Infection of Oral Squamous Cells.2020

    • Author(s)
      Heawchaiyaphum C, Iizasa H, Ekalaksananan T, Burassakarn A, Kiyono T, Kanehiro Y, Yoshiyama H, Pientong C.
    • Journal Title

      Microorganisms

      Volume: 16 Issue: 3 Pages: 419-419

    • DOI

      10.3390/microorganisms8030419

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Corrigendum: Role of Viral and Host microRNAs in Immune Regulation of Epstein-Barr Virus-Associated Diseases.2020

    • Author(s)
      Iizasa H, Kim H, Kartika AV, Kanehiro Y, Yoshiyama H.
    • Journal Title

      Front Immunol.

      Volume: 3 Pages: 498-498

    • DOI

      10.3389/fimmu.2020.00498

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comprehensive prevention of hepatitis B virus to reduce primary liver cancer.2020

    • Author(s)
      Muchtar A, Kartika V, Ding D, Kang Y, Nagoshi K, Kanehiro Y, Iizasa H, Yoshiyama H.
    • Journal Title

      Shimane J Med Sci

      Volume: 37 Pages: 13-20

    • Related Report
      2019 Annual Research Report
  • [Journal Article] ヘルペスウイルス感染症の動向2018

    • Author(s)
      金廣優一、上野詩織、吉山裕規
    • Journal Title

      臨床と研究

      Volume: 95(4) Pages: 1-5

    • Related Report
      2018 Research-status Report
  • [Journal Article] Identification of novel mycobacterial inhibitors against mycobacterial protein kinase G.2018

    • Author(s)
      Kanehiro Y, Tomioka H, Pieters J, Tatano Y, Kim H, Iizasa H, Yoshiyama H.
    • Journal Title

      Frontiers in Microbiology

      Volume: 9 Pages: 1517-1517

    • DOI

      10.3389/fmicb.2018.01517

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 胃内視鏡生検標本を用いた胃炎とEpstein-Barr virusゲノム増幅の関連性の研究2019

    • Author(s)
      Kartika Andy Visi、飯笹 久、梶 俊介、Fekadu Sintayehu、金廣 優一、柳井 秀雄、吉山 裕規
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] B型肝炎ウイルスの増殖を抑制するヒトmiRNAの同定.2019

    • Author(s)
      Amrizal Muchtar、飯笹久、Dan Ding、金廣優一、吉山裕規
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Epstein-Barr virus infection induces mitochondrial DNA mutation through APOBEC3C expression in gastric epithelial cells2019

    • Author(s)
      Yuichi Kanehiro, Hisashi Iizasa, Hironori Yoshiyama
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] EBV-encoded BART miRNA induces HIF-1a-mediated glycolysis by regulating VHL-dependent pathway in head and neck cancer2019

    • Author(s)
      Ati Burassakarn, Hisashi Iizasa, Yuting Kang, Chukkris Heawchaiyaphum, Yuichi Kanehiro, Chamsai Pientong, Tipaya Ekalaksan, Hironori Yoshiyama
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Transcriptional activation of Epstein-Barr virus encoded BART miRNAs in NK/T lymphomas.2018

    • Author(s)
      Hyoji Kim、飯笹久、金廣優一、清水則夫、吉山裕規
    • Organizer
      第66回日本ウイルス学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Biological properties of Epstein-Barr virus positive oral squamous cell carcinoma cell lines2018

    • Author(s)
      Heawchaiyaphum C, Ekalaksananan T, Iizasa H, Kanehiro Y, Kiyono T, Yoshiyama H, Pientong C
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] EBウイルスmiRNAの発現は、ウイルス感染によって誘導された宿主転写因子ETS-Aにより制御される2018

    • Author(s)
      Hyoji Kim、飯笹久、金廣優一、吉山裕規
    • Organizer
      第20回日本RNA学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] EBウイルス関連NK/Tリンパ腫におけるBART miRNA転写活性化について2018

    • Author(s)
      Hyoji Kim、飯笹久、上野詩織、田中星奈、金廣優一、清水則夫、吉山裕規
    • Organizer
      第15回EBウイルス研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] EBウイルス関連NK/Tリンパ腫におけるBART miRNA転写活性化について2018

    • Author(s)
      Hyoji Kim、飯笹久、金廣優一、清水則夫、吉山裕規
    • Organizer
      第32回ヘルペスウイルス研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] EBウイルス陽性口腔扁平上皮癌の実験モデルの構築2018

    • Author(s)
      Chukkris Heawchaiyaphum, Chamsai Pientong, Tipaya Ekalaksananan, 飯笹久, 金廣優一, Amrizal Muhtar, Sintayehu Fekadu, 清野透, 吉山裕規
    • Organizer
      第33 回中国四国ウイルス研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] EBウイルス感染がもたらす胃上皮細胞のミトコンドリアDNA変異2018

    • Author(s)
      金廣優一、飯笹久、Sintayehu Fekadu、上野詩織、吉山裕規
    • Organizer
      平成30年度中四国乳酸菌研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] LMP2A regulates BART miRNAs’ transcription by translational activation of ETS family gene.2018

    • Author(s)
      Kim H, Iizasa H, Kanehiro Y, Yoshiyama H.
    • Organizer
      18thInternational Symposium on EBV and KSHV.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Epstein-Barr virus infection of epithelial cells causes mitochondrial DNA mutation.2018

    • Author(s)
      Kanehiro Y, Kim H, Fekadu S, Iizasa H, Yoshiyama H.
    • Organizer
      The 19th Royal Golden Jubilee Ph.D. Congress `Innovation Challenges toward Thailand 4.0
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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