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Elucidation of the molecular mechanism of medial temporal lobe sclerosis caused by human herpesvirus 6B infection

Research Project

Project/Area Number 19K17346
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionFujita Health University

Principal Investigator

Kawamura Yoshiki  藤田医科大学, 医学部, 講師 (30581475)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywordsヒトヘルペスウイルス6 / ヒトヘルペスウイルス6B / 内側側頭葉硬化症 / 内側側頭葉てんかん / RNA-Seq
Outline of Research at the Start

human herpesvirus 6B(HHV-6B)は乳幼児でよく経験する突発性発疹を初感染で引き起こすウイルスである。初感染時には脳炎・脳症を合併することがあるが、初感染後生体内に潜伏感染し、造血幹細胞移植患者で再活性化し移植後急性辺縁系脳炎も引き起こす。さらに難治性てんかんである側頭葉てんかん(MTLE)発症への関与も示唆されている。MTLEの治療法として海馬切除術があるが、我々はその切除脳組織を用いて海馬・扁桃体に潜伏感染したHHV-6Bとヒトの遺伝子発現を次世代シークエンサーを用いて網羅的に解析することでHHV-6BとMTLEの関与やMTLEの発症メカニズムを明らかにする。

Outline of Final Research Achievements

We showed previously that human herpesvirus 6B (HHV-6B) could be detected in hippocampus and amygdala of patients with medial temporal lobe sclerosis (MTS) which was intractable epilepsy. In this study, gene expression were analyzed in brains of these patients and healthy controls to elucidate the influence of HHV-6B infection in MTS patients. HHV-6B was detected in 22 of 80 hippocampus and 8 of 30 amygdala. Two or three samples each were selected from HHV-6B detected, non-detected, or healthy brains, and next-generation sequencing was performed. In the future, we are going to compare these gene expressions between each group and analyze the influence of HHV-6 infection on the hippocampus and amygdala.

Academic Significance and Societal Importance of the Research Achievements

本研究では先行研究と同様にHHV-6BがMTS患者脳で検出されることが確認され、HHV-6BのMTSへの影響の可能性が再確認された。MTSは抗てんかん薬の内服治療に対して抵抗性であることが多く、現在は手術で海馬、扁桃体を摘出することが有効である。しかしながら、この治療は侵襲性が高く低侵襲かつ有効性の高い治療が望まれている。今後、HHV-6BのMTS発症への関与が明らかにされれば、本症の発症予防あるいは治療として非侵襲的な抗ウイルス薬療法が有効である可能性が提案できると考えられる。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (2 results)

All 2021 2020

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results)

  • [Journal Article] Hippocampal Atrophy in Pediatric Transplant Recipients with Human Herpesvirus 6B2021

    • Author(s)
      Misa Miyake, Yoshiki Kawamura, Naoko Ishihara, Shigetaka Suzuki, Hiroki Miura, Yoko Sakaguchi, Masaharu Tanaka, Yoshiyuki Takahashi, Seiji Kojima, Hiroshi Toyama, Jun Natsume and Tetsushi Yoshikawa
    • Journal Title

      Microorganisms

      Volume: 9 Issue: 4 Pages: 776-776

    • DOI

      10.3390/microorganisms9040776

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical Features of Complex Febrile Seizure Caused by Primary Human Herpesvirus 6B Infection2020

    • Author(s)
      Misa Miyake, Yoshiki Kawamura, Fumihiko Hattori, Hiroki Miura, Naoko Ishihara, Tetsushi Yoshikawa
    • Journal Title

      Pediatric neurology

      Volume: 109 Pages: 52-55

    • DOI

      10.1016/j.pediatrneurol.2020.03.015

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed

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Published: 2019-04-18   Modified: 2022-01-27  

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