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The prediction of the clinical records for infectious diseases by tracking the diversity of Immuoglobulin gene mutation

Research Project

Project/Area Number 16K14650
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Medical genome science
Research InstitutionNational Institutes of Biomedical Innovation, Health and Nutrition

Principal Investigator

YASUI TERUHITO  国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 感染症制御プロジェクト, プロジェクトリーダー (60283074)

Co-Investigator(Kenkyū-buntansha) 奥崎 大介  大阪大学, 微生物病研究所, 助教 (00346131)
南谷 武春  国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 感染症制御プロジェクト, プロジェクト研究員 (00374679)
中村 昇太  大阪大学, 微生物病研究所, 特任准教授(常勤) (90432434)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsイムノグロブリン / 体細胞突然変異 / 破傷風毒素 / サイトメガロウイルス / 次世代シークエンサー / 感染症 / 遺伝子
Outline of Final Research Achievements

Human acquired immune responses includes B cell differentiation in which immunoglobulin (Ig) genes undergo somatic mutations against pathogen infection. However, it has not been understood how fast and ordered Ig gene got mutations in response to the infections. To elucidate molecular mechanisms in which the human immune responses regulates Ig affinity, pathogen-induced Ig gene mutation was analyzed with molecular biological approach. As a result, we were able to identify the numbers and hot spots in the Ig gene mutations induced by vaccine components, and viral proteins derived from persistent infections. Collectively, the findings in this project indicate persistently viral infection always maintains the humoral immune responses through the continuous stimulation by viral proteins that the reactivation provides in human.

Academic Significance and Societal Importance of the Research Achievements

ヒトにおける感染に関する疫学的調査と、抗体遺伝子変異解析や抗体親和性解析といった、分子生物学的アプローチによってなされる融合研究である。一方、抗体遺伝子変異解析によって得られた知見を基に、規則性が見いだせれば、環境応答と遺伝子変異の相関性といった生命科学に新たなパラダイムを生むこととなる。また病原体にいつ感染したのかという予想が行えれば、本研究成果の発展型として、網羅的なIg遺伝子変異による「感染プロファイル」が可能となる。

Report

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

    (32 results)

All 2019 2018 2017 2016

All Journal Article (14 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 13 results,  Open Access: 8 results,  Acknowledgement Compliant: 5 results) Presentation (18 results) (of which Int'l Joint Research: 3 results,  Invited: 6 results)

  • [Journal Article] Bystander inhibition of humoral immune responses by Epstein-Barr virus LMP1.2018

    • Author(s)
      Tsai C.-Y., Sakakibara S., Yasui T., Minamitani T., Okuzaki D., and Kikutani H.
    • Journal Title

      International Immunology

      Volume: 30(12) Issue: 12 Pages: 579-90

    • DOI

      10.1093/intimm/dxy053

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Murine γ-Herpesvirus 68 Induces Severe Lung Inflammation in IL-27-Deficient Mice with Liver Dysfunction Preventable by Oral Neomycin.2018

    • Author(s)
      Kyosuke Kanai, Ah-Mee Park, Akiko Watanabe, Tomohiro Arikawa, Teruhito Yasui, Hiroki Yoshida, Ikuo Tsunoda and Osamu Yoshie.
    • Journal Title

      J Immunol

      Volume: 200 Issue: 8 Pages: 2703-2713

    • DOI

      10.4049/jimmunol.1700412

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] A mouse model of Epstein-Barr virus LMP1 and LMP2A driven germinal center B-cell lymphoproliferative disease.2017

    • Author(s)
      1Minamitani, T., Ma, Y., Zhou, H., Kida, H., Tsai, C.-Y., Obana, M., Okuzaki, D., Fujio, Y., Kumanogoh, A., Kikutani, H., Zhao, B., Kieff, E., Gewuz, B. E., Yasui, T.
    • Journal Title

      Proc. Natl. Acad. Sci. USA.

      Volume: 印刷中 Issue: 18 Pages: 4751-4756

    • DOI

      10.1073/pnas.1701836114

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 自己免疫疾患発症とEBウイルス由来蛋白LMP2A2017

    • Author(s)
      南谷武春、安居輝人
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 68 Pages: 334-340

    • NAID

      40021318897

    • Related Report
      2017 Research-status Report
  • [Journal Article] Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment.2017

    • Author(s)
      Kitagawa Y, Ohkura N, Kidani Y, Vandenbon A, Hirota K, Kawakami R, Yasuda K, Motooka D, Nakamura S, Kondo M, Taniuchi I, Kohwi-Shigematsu T, Sakaguchi S.
    • Journal Title

      Nat Immunol.

      Volume: 18(2) Issue: 2 Pages: 173-183

    • DOI

      10.1038/ni.3646

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Argininosuccinate Synthase 1-Deficiency Enhances the Cell Sensitivity to Arginine through Decreased DEPTOR Expression in Endometrial Cancer.2017

    • Author(s)
      Ohshima K, Nojima S, Tahara S, Kurashige M, Hori Y, Hagiwara K, Okuzaki D, Oki S, Wada N, Ikeda JI, Kanai Y, Morii E.
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 45504-45504

    • DOI

      10.1038/srep45504

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] BATF2 inhibits immunopathological Th17 responses by suppressing Il23a expression during Trypanosoma cruzi infection.2017

    • Author(s)
      Kitada S, Kayama H, Okuzaki D, Koga R, Kobayashi M, Arima Y, Kumanogoh A, Murakami M, Ikawa M and Takeda K
    • Journal Title

      J. Exp. Med.

      Volume: 印刷中 Issue: 5 Pages: 1313-1331

    • DOI

      10.1084/jem.20161076

    • NAID

      120006957435

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Crystal structure of the ADP-ribosylating component of BEC, the binary enterotoxin of Clostridium perfringens.2016

    • Author(s)
      Kawahara K, Yonogi S, Munetomo R, Oki H, Yoshida T, Kumeda Y, Matsuda S, Kodama T, Ohkubo T, Iida T, Nakamura S
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 480 Issue: 2 Pages: 261-267

    • DOI

      10.1016/j.bbrc.2016.10.042

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The RNA Binding Protein Mex-3B Is Required for IL-33 Induction in the Development of Allergic Airway Inflammation.2016

    • Author(s)
      Yamazumi Y, Sasaki O, Imamura M, Oda T, Ohno Y, Shiozaki-Sato Y, Nagai S, Suyama S, Kamoshida Y, Funato K, Yasui T, Kikutani H, Yamamoto K, Dohi M, Koyasu S, Akiyama T.
    • Journal Title

      Cell Rep.

      Volume: 16 Issue: 9 Pages: 2456-2471

    • DOI

      10.1016/j.celrep.2016.07.062

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine.2016

    • Author(s)
      Maeda Y, Kurakawa T, Umemoto E, Motooka D, Ito Y, Gotoh K, Hirota K, Matsushita M, Furuta Y, Narazaki M, Sakaguchi N, Kayama H, Nakamura S, Iida T, Saeki Y, Kumanogoh A, Sakaguchi S, and Takeda K
    • Journal Title

      Arthritis Rheum

      Volume: 68 Issue: 11 Pages: 2646-2661

    • DOI

      10.1002/art.39783

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Herpes zoster laryngitis in a patient treated with fingolimod.2016

    • Author(s)
      Hagiya H, Yoshida H, Shimizu M, Motooka D, Nakamura S, Iida T, Yamamoto N, Akeda Y, Tomono K.
    • Journal Title

      J Infect Chemother.

      Volume: 22 Issue: 12 Pages: 830-832

    • DOI

      10.1016/j.jiac.2016.07.011

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Homo-trimeric Structure of the Type IVb Minor Pilin CofB Suggests Mechanism of CFA/III Pilus Assembly in Human Enterotoxigenic Escherichia coli.2016

    • Author(s)
      Kawahara K, Oki H, Fukakusa S, Yoshida T, Imai T, Maruno T, Kobayashi Y, Motooka D, Iida T, Ohkubo T, Nakamura S.
    • Journal Title

      J Mol Biol.

      Volume: 428 Issue: 6 Pages: 1209-26

    • DOI

      10.1016/j.jmb.2016.02.003

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Polarization of M2 macrophages requires Lamtor1 that integrates cytokine and amino-acid signals2016

    • Author(s)
      Kimura T, Nada S, Takegahara N, OkunoT, NojimaS, Kang S, Ito D, Morimoto K, Morimoto K, Hosokawa T, Hayama Y, Mitsui Y, Sakurai N, Sarashina-Kida H, Nishide M, Maeda Y, Takamatsu H, Okuzaki D, Yamada M, Okada M, Kumanogoh A.
    • Journal Title

      Nat Commun.

      Volume: 7 Issue: 1 Pages: 13130-13130

    • DOI

      10.1038/ncomms13130

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microarray and whole-exome sequencing analysis of familial Behcet's disease patients.2016

    • Author(s)
      Okuzaki D, Yoshizaki K, Tanaka T, Hirano T, Fukushima K, Washio T, Nojima H.
    • Journal Title

      Sci Rep.

      Volume: 20 Issue: 1 Pages: 19456-19456

    • DOI

      10.1038/srep19456

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] ヒトリキッドバイオプシーから臨む診断薬/治療抗体シーズの情報集積技術2019

    • Author(s)
      安居輝人
    • Organizer
      富山県薬事講演会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ヒト免疫原性を基盤としたバイオロジクス開発戦略2019

    • Author(s)
      安居輝人
    • Organizer
      第12回次世代アジュバント研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ワクチンターゲット探索へ向けた網羅的ヒト免疫原性解析2019

    • Author(s)
      南谷武春
    • Organizer
      第12回次世代アジュバント研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] EBウイルスLMPシグナルによる節外性リンパ腫形成2018

    • Author(s)
      安居輝人
    • Organizer
      第15回EBウイルス学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] CMVに対する網羅的ヒト免疫原性解析2018

    • Author(s)
      南谷武春、古田里佳、今留謙一、安居輝人
    • Organizer
      ヘルペスウイルス研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] サイトメガロウイルスの網羅的ヒト免疫原性解析2018

    • Author(s)
      南谷武春、古田里佳、今留謙一、安居輝人
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Concurrent expression of EBV LMP1 and LMP2A in germinal center B cells induces lymphomagenesis in mouse model2018

    • Author(s)
      Takeharu Minamitani,
    • Organizer
      International Conference on EBV & KSHV 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト免疫機構を基盤とした免疫駆動型バイオロジクス ―ワクチンターゲット探索と感染症関連抗体医薬品開発―2018

    • Author(s)
      安居輝人
    • Organizer
      平成29年度第3回「ワクチン用新規アジュバント開発のための基盤研究プロジェクト」進捗状況報告会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] ヒト免疫原性に基づいた感染症関連バイオロジクス探索技術2018

    • Author(s)
      安居輝人
    • Organizer
      メディカルジャパン2018大阪「関西広域連合研究成果企業化促進セミナー」
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] ウイルス感染が誘導する自己免疫疾患2017

    • Author(s)
      南谷武春
    • Organizer
      第24回日本免疫毒性学会学術年会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 胚中心B細胞におけるEBウイルスLMP1とLMP2Aの協調的発現がリンパ増殖性疾患を誘導する2017

    • Author(s)
      南谷武春、安居輝人
    • Organizer
      第31回ヘルペスウイルス研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] EBウイルスLMP1とLMP2Aの協調的発現はT/NK細胞と競合的にリンパ腫プロセスを誘導する2017

    • Author(s)
      南谷武春、Yijie Ma、Hufeng Zhou、木田博、Chao-Yan Tsai、尾花理徳、奥崎大介、藤尾慈、熊ノ郷淳、Bo Zhao、菊谷仁、Elliott Keff、Benjamin E. Gewurz、安居輝人
    • Organizer
      第14回EBウイルス研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] EBV LMP1 and LMP2A coordinately induce EBV-associated lymphoproliferative diseases in mouse model.2017

    • Author(s)
      南谷武春、Yijie Ma、木田博、Chao-Yuan Tsai、尾花理徳、奥崎大介、藤尾慈、熊ノ郷淳、菊谷仁、Elliott Kieff、Benjamin E. Gewurz、安居輝人
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] The concerted impact of Epstein-Barr Virus LMP1 and LMP2A on the virus-induced lymphoproliferative diseases in mouse model.2017

    • Author(s)
      Takeharu Minamitani, Yjie Ma, Hufeng Zhou, Hiroshi Kida, Chao-Yuan Tsai, Masanori Obana, Daisuke Okuzaki, Yasushi Fujio, Atsushi Kumanogoh, Bo Zhao, Hiroshi Kikutani, Elliott Kieff, Benjamin E Gewurz, Terihito Yasui.
    • Organizer
      第42回国際ヘルペスウイルスワークショップ2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] EBウイルスによるリンパ増殖性疾患発症機構の解明2017

    • Author(s)
      安居輝人
    • Organizer
      第13回霊長類医科学フォーラム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] B cell-specific simultaneous expression of EB virus LMP1 and LMP2A induces lethal lymphoproliferative. pathogenesis in murine model.2016

    • Author(s)
      Takeharu Minamitani, Chiau-Yuang Tsai, Hitoshi Kikutani and Teruhito Yasui
    • 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] Epstein-Barr virus LMP2A modifies the affinity-based selection of B cells in germinal centers.2016

    • Author(s)
      Takeharu Minamitani, Teruhito Yasui, Yijie Ma, Hufeng Zhou, Daisuke Okuzaki, Chiau-Yuang Tsai, Shuhei Sakakibara, Benjamin E. Gewurz, Elliott Kieff and Hitoshi Kikutani
    • Organizer
      17th International Symposium on EBV and associated diseases
    • Place of Presentation
      スイス、チューリッヒ
    • Year and Date
      2016-08-08
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] LIPS/DDP 法を用いた EBV のヒト免疫原性探索2016

    • Author(s)
      南谷武春、古田里佳、河 敬世、安居輝人
    • Organizer
      第30回ヘルペスウイルス研究会
    • Place of Presentation
      東京
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report

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

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