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Research of activation mechanism and pathogenicity of CIHHV-6

Research Project

Project/Area Number 20K17460
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Endo Akifumi  東京医科歯科大学, 東京医科歯科大学病院, プロジェクト助教 (80624238)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsCIHHV-6 / HHV-6 / immunodeficiency
Outline of Research at the Start

Human herpesvirus-6(HHV-6)は、けいれん発作や脳炎などに関わるDNAウイルスである。1990年代にこのHHV-6 がヒトゲノムの生殖細胞系に組み込まれる事(Chromosomally integrated HHV-6:CIHHV-6)が発見され、その後人口の約1%が保持している事が分かってきた。研究者は、このCIHHV-6が体内で活性化し病原性を有する事をウイルス学的および分子生物学的に確認し報告してきた。しかし詳細な活性化機構は未だ解明されておらず、またHHV-6が組み込まれる機構も未解明のままである。本研究では、これらの機構の解明を目指している。

Outline of Final Research Achievements

In this study, we aimed to elucidate the activation mechanism of CIHHV-6. We collected clinical information and samples from patients with CIHHV-6. We constructed an immunodeficiency registry in Japan, identified CIHHV-6 patients, and collected clinical specimens and clinical information. Also, during the research period, the social impact of COVID-19 was significant, so we cooperated with those studies. In our case of CIHHV-6, activation was observed in an immunodeficient patient with a single-gene IL2RG abnormality, and in order to verify whether the corresponding gene was involved in the activation mechanism, an immortalized cell line was established from the patient's family specimen. We studied the establishment of a system that knocks down IL2RG.But it is difficult to establish the system, and we are examining the conditions.

Academic Significance and Societal Importance of the Research Achievements

CIHHV-6患者さんを含んだ本邦の免疫不全レジストリを構築することができた。
また研究期間中はCOVID-19の社会的影響が大きかったため、それらの研究へ貢献した。CIHHV-6 症例からもEBVによる不死化細胞株の樹立が確認できた。
しかしノックダウンする系の立ち上げは通常の細胞よりも難しいことが確認された。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (7 results)

All 2022 2021 2020

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

  • [Journal Article] The Primary Immunodeficiency Database in Japan2022

    • Author(s)
      Mitsui-Sekinaka Kanako、Sekinaka Yujin、Endo Akifumi、Imai Kohsuke、Nonoyama Shigeaki
    • Journal Title

      Frontiers in Immunology

      Volume: 12 Pages: 805766-805766

    • DOI

      10.3389/fimmu.2021.805766

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neutralizing Type I Interferon Autoantibodies in Japanese Patients with Severe COVID-192022

    • Author(s)
      Eto S, Nukui Y, Tsumura M, Nakagama Y, Kashimada K, Mizoguchi Y, Utsumi T, Taniguchi M, Sakura F, Noma K, Yoshida Y, Ohshimo S, Nagashima S, Okamoto K, Endo A, Imai K, Kanegane H, Ohnishi H, Hirata S, Sugiyama E, Shime N, Ito M, Ohge H, Kido Y, Bastard P, Casanova JL, Ohara O, Tanaka J, Morio T, Okada S
    • Journal Title

      Journal of Clinical Immunology

      Volume: 42 Issue: 7 Pages: 1360-1370

    • DOI

      10.1007/s10875-022-01308-3

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force2022

    • Author(s)
      Wang Qingbo S.、et al.
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 4830-4830

    • DOI

      10.1038/s41467-022-32276-2

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-192021

    • Author(s)
      Asano Takaki、Boisson Bertrand、Onodi Fanny, et al.
    • Journal Title

      Science Immunology

      Volume: 6 Issue: 62

    • DOI

      10.1126/sciimmunol.abl4348

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hematopoietic Cell Transplantation with Reduced Intensity Conditioning Using Fludarabine/Busulfan or Fludarabine/Melphalan for Primary Immunodeficiency Diseases2021

    • Author(s)
      Nishimura Akira、Aoki Yuki、Ishiwata Yasuyoshi、・・・Endo Akifumi、Yasuhara Masato、Kamiya Takahiro、Mitsuiki Noriko、Ono Toshiaki、Isoda Takeshi、Yanagimachi Masakatsu、Tomizawa Daisuke、Nagasawa Masayuki、Mizutani Shuki、Kajiwara Michiko、Takagi Masatoshi、Kanegane Hirokazu、Imai Kohsuke、Morio Tomohiro
    • Journal Title

      Journal of Clinical Immunology

      Volume: 41 Issue: 5 Pages: 944

    • DOI

      10.1007/s10875-021-00966-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association between Immunoglobulin M and Steroid Resistance in Children with Nephrotic Syndrome: A Retrospective Multicenter Study in Japan2021

    • Author(s)
      Udagawa T, Matsuyama Y, Okutsu M, Motoyoshi Y, Okada M, Tada N, Kikuchi E, Shimoda M, Kanamori T, Omori T, Takahashi M, Imai K,Endo A, Fujiwara T and Morio T
    • Journal Title

      Kidney360

      Volume: 2021 Issue: 3 Pages: 487-493

    • DOI

      10.34067/kid.0004432020

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cytomegalovirus Laryngitis in Primary Combined Immunodeficiency Diseases2020

    • Author(s)
      Inoue Maiko、Isoda Takeshi、Yamashita Motoi、Tomoda Takahiro、Inoue Kento、Okano Tsubasa、Ohkawa Teppei、Endo Akifumi、Mitsuiki Noriko、Kamiya Takahiro、Yanagimachi Masakatsu、Yamamoto Kouhei、Inaba Yuichiro、Sasaki Toru、Takagi Masatoshi、Kanegane Hirokazu、Imai Kohsuke、Morio Tomohiro
    • Journal Title

      Journal of Clinical Immunology

      Volume: 41 Issue: 1 Pages: 243-247

    • DOI

      10.1007/s10875-020-00873-9

    • Related Report
      2020 Research-status Report
    • Peer Reviewed

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Published: 2020-04-28   Modified: 2024-01-30  

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