Elucidation of Pathogenesis and Development of Therapeutic Strategies for Severe Pneumonia Caused by MERS-CoV Using an Infected Animal Model
Project/Area Number |
19K08945
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54030:Infectious disease medicine-related
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Research Institution | National Institute of Infectious Diseases |
Principal Investigator |
Naoko Iwata 国立感染症研究所, 感染病理部, 主任研究官 (10360695)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | 動物モデル / コロナウイルス / 治療法 |
Outline of Research at the Start |
MERS-CoVの本来の病原性は軽度の風邪を起こす程度のものであり重症化するには宿主側かウイルス側、あるいはその両方に原因がある。そこで、感染動物モデルを用いて、宿主側(マウス側)あるいはウイルス側を変化させて、MERS-CoVの重症肺炎の機序を探る。最終的には重症かの原因を特定し、病原性の解明、治療薬の開発、治療法の解明につなげる。
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Outline of Final Research Achievements |
MERS-CoV, a respiratory infection, causes pneumonia that is more likely to be severe in people with underlying medical conditions. The mechanism underlying its severe progression remains unknown, and the development of treatments and vaccines is still in progress. In this study, we established a severe pneumonia model using transgenic (Tg) mice expressing MERS-CoV receptors to investigate the differences between severe progression and recovery, aiming to elucidate the underlying mechanisms. Since reports suggested that reduced type 1 and type 2 IFNs contributed to the severe disease, we administered anti-IFNAR1 and anti-IFNγ antibodies to Tg mice to reduce inflammation, and then attempted to infect them with MERS-CoV. The mice showed an effect on body weight change, but did not become severely ill. It was clear that other factors in addition to inflammation were necessary for severe disease.
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Academic Significance and Societal Importance of the Research Achievements |
本研究は、MERS-CoVの重症化メカニズムを解明し、感染制御や治療法の開発に貢献する学術的な意義がある。また、type 1およびtype 2 IFNの低下が重症化の要因と示唆され、炎症以外の要素も関与していることが明らかとなった。MERS-CoV感染症への理解が深まり、将来的な予防策や治療法の開発につながる可能性がある。これにより、感染症対策や公衆衛生政策の向上に貢献することが期待される。
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Report
(3 results)
Research Products
(16 results)
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[Journal Article] Essential role of TMPRSS2 in SARS-CoV-2 infection in murine airways2022
Author(s)
Iwata-Yoshikawa N, Kakizaki M, Shiwa-Sudo N, Okura T, Tahara M, Fukushi S, Maeda K, Kawase M, Asanuma H, Tomita Y, Takayama I, Matsuyama S, Shirato K, Suzuki T, Nagata N, Takeda M.
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Journal Title
Nat Commun . 2
Volume: 13
Issue: 1
Pages: 6100-6100
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Gold nanoparticle-adjuvanted S protein induces a strong antigen-specific IgG response against severe acute respiratory syndrome-related coronavirus infection, but fails to induce protective antibodies and limit eosinophilic infiltration in lungs.2019
Author(s)
Hanako Sekimukai, Naoko Iwata-Yoshikawa, Shuetsu Fukushi, Hideki Tani, Michiyo Kataoka, Tadaki Suzuki, Hideki Hasegawa, Kenichi Niikura, Katsuhiko Arai, Noriyo Nagata.
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Journal Title
Microbiology and Immunology
Volume: 64
Issue: 1
Pages: 33-51
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] マウスモデルを用いたSARS-CoV-2感染におけるTMPRSS2の役割についての解析.2022
Author(s)
岩田 (吉河) 奈織子, 柿崎正敏, 志和 希, 大倉 喬, 田原舞乃, 福士秀悦, 前田 健, 川瀬みゆき, 冨田有里子, 高山郁代, 松山州徳, 白戸憲也, 鈴木忠樹, 竹田 誠, 永田典代.
Organizer
第69回日本ウイルス学会 (長崎)
Related Report
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[Presentation] SARS-CoV-2 の懸念される変異株 (VOCs) の性質解析.2022
Author(s)
柿崎正敏、岩田 (吉河) 奈織子, 志和 希, 大倉 喬, 田原舞乃, 福士秀悦, 前田 健, 冨田有里子, 高山郁代, 松山州徳, 白戸憲也, 鈴木忠樹, 永田典代、竹田 誠.
Organizer
第69回日本ウイルス学会 (長崎)
Related Report
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