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Study for the establishment of preventive measures to sensorineural healing loss with congenital cytomegalovirus infection

Research Project

Project/Area Number 17H04346
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionFukushima Medical University

Principal Investigator

Suzutani Tatsuo  福島県立医科大学, 医学部, 教授 (40196895)

Co-Investigator(Kenkyū-buntansha) 小林 敬広  福島県立医科大学, 医学部, 助教 (00708745)
宮崎 希  福島県立医科大学, 医学部, 助教 (40725876)
石岡 賢  福島県立医科大学, 医学部, 講師 (50305356)
小川 洋  福島県立医科大学, 公私立大学の部局等, 教授 (70264554)
腰塚 哲朗  福島県立医科大学, 医学部, 講師 (20416267)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywordsサイトメガロウイルス / 先天性サイトメガロウイルス感染 / 聴覚障害 / 慢性炎症 / ステロイドホルモン / 病態生理 / 外有毛細胞 / 鼓室内投与 / ステロイド / 先天感染 / 水痘-帯状疱疹ウイルス / 弱毒化 / 感染症 / 臨床検査 / 先天性サイトメガロウイルス感染症 / トロピズム / 薬剤スクリーニング / ウイルス
Outline of Final Research Achievements

Congenital cytomegalovirus (CMV) infection is a one of the leading causes for sensorineural hearing loss. As a countermeasure against this disease, we established a screening method for the development of a new drug and studied the pathogenesis in a mouse experimental model.
For screening of anti-CMV drug, a recombinant CMV, inserted the secretable Metridia luciferase gene under UL146 promotor, was constructed. As predicted, luciferase activity was secreted into the culture medium and correlated with virus replication in host cells. Using the virus strain, we established a screening system for anti-CMV compounds.
We evaluated the effects of steroids, as an anti-inflammatory compound, on the progression of hearing loss in a mouse congenital CMV infection model. Topical treatment by intratympanic cavity injection of dexamethasone improved hearing loss significantly, suggesting a new treatment strategy for hearing loss induced by congenital CMV infection.

Academic Significance and Societal Importance of the Research Achievements

先天性サイトメガロウイルス感染はもっとも頻度の高い先天感染で、日本人では300の出生に1例起こる感染である。その20%程度では言語獲得期以前の両側性難聴が起こり、聴覚障害の原因の15%を占めることが明らかとなっている。この頻度の高い疾患の治療法の開発や発症予防法の確立は強く社会から求められてる課題である。本研究はこの要請に応じるべく、治療薬のスクリーニング法の確立や病態生理に基づいた新たな治療法の可能性を検討したもので、社会的な意義は大きい。
また、内耳の炎症を抑えることで聴覚障害の進行が抑えられることを示した点は、これからの聴覚障害についての学術的な研究に広く示唆を与えられるものである。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (13 results)

All 2020 2019 2018 2017

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (6 results) (of which Invited: 3 results)

  • [Journal Article] A case of congenital herpes simplex virus infection diagnosed at 8?months of age2020

    • Author(s)
      Yamamoto Shiho、Nagamori Tsunehisa、Komatsu Shigetsuna、Shirai Masaru、Suzutani Tatsuo、Oki Junichi
    • Journal Title

      Brain and Development

      Volume: 42 Issue: 4 Pages: 369-372

    • DOI

      10.1016/j.braindev.2020.01.003

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of the indirect and IgM‐capture anti‐human cytomegalovirus IgM ELISA methods as confirmed by cytomegalovirus IgG avidity2019

    • Author(s)
      Ikuta Kazufumi、Koshizuka Tetsuo、Kanno Ryoko、Inoue Naoki、Kubo Takahiko、Koyano Shin、Suzutani Tatsuo
    • Journal Title

      Microbiology and Immunology

      Volume: 63 Issue: 5 Pages: 172-178

    • DOI

      10.1111/1348-0421.12683

    • NAID

      40021927513

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of engraftment of donor-derived antibody producing cells in a lung transplant recipient by anti-cytomegalovirus IgG avidity test2019

    • Author(s)
      Koshizuka Tetsuo、Matsuda Yasushi、Suzuki Hirotoshi、Kanno Ryoko、Ikuta Kazufumi、Kobayashi Takahiro、Kondo Takashi、Okada Yoshinori、Suzutani Tatsuo
    • Journal Title

      Transplant Immunology

      Volume: 53 Pages: 34-37

    • DOI

      10.1016/j.trim.2018.12.003

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Herpesviruses possess conserved proteins for interaction with Nedd4 family ubiquitin E3 ligases.2018

    • Author(s)
      Koshizuka T, Kobayashi T, Ishioka K, Suzutani T.
    • Journal Title

      Sci Rep.

      Volume: 8(1) Issue: 1 Pages: 4447-4447

    • DOI

      10.1038/s41598-018-22682-2

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A two-step culture method utilizing secreted luciferase recombinant virus for detection of anti-cytomegalovirus compounds2018

    • Author(s)
      Koshizuka Tetsuo、Sato Yuko、Kobiyama Shoe、Oshima Mami、Suzutani Tatsuo
    • Journal Title

      Microbiology and Immunology

      Volume: 62 Issue: 10 Pages: 651-658

    • DOI

      10.1111/1348-0421.12645

    • NAID

      40021702623

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Congenital cytomegalovirus infection via a re-infected mother with original antigenic sin: A case report2018

    • Author(s)
      Koshizuka Tetsuo、Toriyabe Kuniaki、Sato Yuko、Ikuta Kazufumi、Ikeda Tomoaki、Suzutani Tatsuo
    • Journal Title

      International Journal of Infectious Diseases

      Volume: 77 Pages: 87-89

    • DOI

      10.1016/j.ijid.2018.10.006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modification of the HCMV-specific IFN-γ release test (QuantiFERON-CMV) and a novel proposal for its application2017

    • Author(s)
      Kobayashi T, Sato J, Ikuta K, Kanno R, Nishiyama K, Koshizuka T, Ishioka K, Suzutani T.
    • Journal Title

      FUKUSHIMA JOURNAL OF MEDICAL SCIENCE

      Volume: 63 Issue: 2 Pages: 64-74

    • DOI

      10.5387/fms.2017-01

    • NAID

      130005966807

    • ISSN
      0016-2590, 2185-4610
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 抗サイトメガロウイルス薬スクリーニングシステムの構築2018

    • Author(s)
      錫谷達夫
    • Organizer
      第28回抗ウイルス療法学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A method for detection of anti-cytomegalovirus compounds with secreted luciferase recombinant virus.2018

    • Author(s)
      Koshizuka T, Sato Y, Kobiyama S, Oshima M, Suzutani T.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] サイトメガロウイルス感染を再考する2018

    • Author(s)
      錫谷達夫
    • Organizer
      熊本血液コロキウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ヘルペスウイルスに共通した宿主ユビキチンリガーゼ制御機構2017

    • Author(s)
      腰塚哲朗、小林敬広、森康子、錫谷達夫
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] サイトメガロウイルス感染症の発症病理2017

    • Author(s)
      錫谷達夫
    • Organizer
      第51回日本実験動物技術者協会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] サイトメガロウイルス感染症 ~感染疫学と難聴の発症病理~2017

    • Author(s)
      錫谷達夫
    • Organizer
      第35回日本耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2017 Annual Research Report
    • Invited

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Published: 2017-04-28   Modified: 2021-02-19  

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