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Mechanism of neurodevelopmental disabilities caused by congenital cytomegalovirus infection

Research Project

Project/Area Number 16K10118
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionNational Center for Child Health and Development

Principal Investigator

Nakamura Hiroyuki  国立研究開発法人国立成育医療研究センター, 免疫アレルギー・感染研究部, 室長 (70256866)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsサイトメガロウイルス / CMV / 神経障害 / 先天性CMV感染症 / SLITRK6 / 難聴 / IE2 / 母子感染 / 神経学的障害 / 先天性サイトメガロウイルス感染症 / 細胞障害 / 神経学的合併症 / iPS細胞 / 母児感染
Outline of Final Research Achievements

Congenital cytomegalovirus (CMV) infection causes sensorineural hearing loss and neurodevelopmental impairment. To understand the molecular mechanism of neuropathogenesis of CMV, we tried to identify novel cellular gene products which may be involved in the CMV neuropathogenesis. We experimentally reproduced CMV-induced neural damages in vitro using human neural cell lines infected with CMV Towne strain or AD169 strain. We analyzed cellular gene expression affected by CMV infection and identified SLITRK6 whose expression was significantly downregulated by CMV infection. We also clarified that the downregulation of SLITRK6 expression by CMV was mediated by CMV-encoded IE2.

Academic Significance and Societal Importance of the Research Achievements

先天性CMV感染症では、難聴や精神発達遅滞などの神経・感覚器障害をともなうが、その発症メカニズムについては不明な点が多い。本研究は、ヒト神経系培養細胞を用いたCMV感染モデルの確立とその活用により、神経・感覚器障害の発症メカニズムの解明を目指すとともに、得られた知見をCMV病原性の制御に向けた新たな方法の開発へ結びつけることを目標とした。本研究成果は、CMVによる神経・感覚器障害に関与する新規細胞遺伝子産物の同定を介してCMV病原性発症メカニズムの理解を深めるとともに、CMV神経病原性の新規制御法を確立する上でも有用な情報になると考えられる。

Report

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

    (5 results)

All 2018 2017 2016 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (3 results) Remarks (1 results)

  • [Journal Article] Human cytomegalovirus downregulates SLITRK6 expression through IE2.2017

    • Author(s)
      Liao H, Sato H, Chiba R, Kawai T, Nakabayashi K, Hata K, Akutsu H, Fujiwara S, Nakamura H.
    • Journal Title

      Journal of Neurovirology

      Volume: 23 Issue: 1 Pages: 79-86

    • DOI

      10.1007/s13365-016-0475-y

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒトサイトメガロウイルスはIE2を介して難聴原因遺伝子SLITRK6の発現を抑制する2018

    • Author(s)
      廖 華南、渡邉拓実、藤原成悦、中村浩幸
    • Organizer
      第32回ヘルペスウイルス研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Innate immune response to Rubella virus infection in human neural cells2018

    • Author(s)
      Huanan Liao, Takumi, Watanabe, Shigeyoshi Fujiwara, Nakamura Hiroyuki
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Human cytomegalovirus infection downregulates the expression of SLITRK6, one of causative genes for hereditary sensorineural hearing loss.2016

    • Author(s)
      Hiroyuki Nakamura, Huanan Liao, Shigeyoshi Fujiwara.
    • 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
  • [Remarks] 研究所サイトマップ

    • URL

      https://www.ncchd.go.jp/sitemap-research.html

    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2022-01-27  

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