Study of mechanisms of viral PLAMP production and PLAMP-mediated regulation of pathogenicity
| Project Area | Establishment of PLAMP as a new concept to determine self and nonself for obligatory intracellular pathogens |
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| Project/Area Number |
20H05773
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| Research Category |
Grant-in-Aid for Transformative Research Areas (B)
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| Allocation Type | Single-year Grants |
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| Review Section |
Transformative Research Areas, Section (III)
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2020-10-02 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥46,150,000 (Direct Cost: ¥35,500,000、Indirect Cost: ¥10,650,000)
Fiscal Year 2022: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2021: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2020: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
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| Keywords | 膜融合 / 構造 / エントリー / PLAMP / ウイルス学 / 構造生物学 / 自己・非自己 |
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| Outline of Research at the Start |
ウイルスは単独では増えることが出来ず、細胞のシステムと一体化することでウイルス自身の増殖を可能にする生存戦略をとっている。すなわち、細胞への侵入(自己化)と細胞からの出芽(非自己化)という過程があり、ウイルスを含む微生物は自身のライフサイクルによって生じる宿主由来分子パターンを細胞上に作り出す。
そこで、本研究では、呼吸器感染症を起こすウイルスをモデル微生物として、分子・細胞 生物学、構造生物学、免疫学、実験動物学の技術を中心とした解析を行い、ウイルス感染に伴う宿主側のミクロな変化を宿主自身が如何にして感知・制御するのか、病原性制御機構の解明を行う。
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| Outline of Final Research Achievements |
In order to elucidate the pathogenic regulatory mechanisms mediated by PLAMP (Pathogen "Life cycle"-Associated Molecular Pattern) during viral infection (cell entry by membrane fusion and budding by membrane fission) using paramyxoviruses and coronaviruses, a combination strategy of structural biology and virological methods were used. As the results, we observed that IFN-inducible molecules, host-derived ligand-like molecules, and carbohydrate chains affect cell entry.
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| Academic Significance and Societal Importance of the Research Achievements |
パラミクソウイルス科は、麻疹（はしか）を起こす麻疹ウイルスや流行性耳下腺炎（おたふくかぜ）の原因であるムンプスウイルスを、コロナウイルス科は重症肺炎などを起こす新型コロナウイルスといった臨床上重要な病原体を含む。従って、これらのウイルスにおけるPLAMPを通じた病原性の理解とその感染制御に関する研究を行うことは、ウイルスへの学問的な理解だけに留まらず、予防・治療法への活用を含めた感染対策として医療や福祉にも貢献が期待できる。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Structural basis of spike RBM-specific human antibodies counteracting broad SARS-CoV-2 variants2023
Author(s)
Kiyomi Shitaoka, Akifumi Higashiura, Yohei Kawano, Akima Yamamoto, Yoko Mizoguchi, Takao Hashiguchi , Norihisa Nishimichi, Shiyu Huang, Ayano Ito, Shun Ohki, Miyuki Kanda, Tomohiro Taniguchi, Rin Yoshizato, Hitoshi Azuma, Yasuo Kitajima, Yasuyuki Yokosaki, Satoshi Okada, Takemasa Sakaguchi, Tomoharu Yasuda
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Journal Title
Communications Biology
Volume: 6
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A SARS-CoV-2 antibody broadly neutralizes SARS-related coronaviruses and variants by coordinated recognition of a virus-vulnerable site2021
Author(s)
Onodera T, Kita S, Adachi Y, Moriyama S, Sato A, Nomura T, Sakakibara S, Inoue T, Tadokoro T, Anraku Y, Yumoto K, Tian C, Fukuhara H, Sasaki M, Orba Y, Shiwa N, Iwata N, Nagata N, Suzuki T, others, and Takahashi Y
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Journal Title
Immunity
Volume: 54
Issue: 10
Pages: 2385-2398
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Resistance of SARS-CoV-2 variants to neutralization by antibodies induced in convalescent patients with COVID-192021
Author(s)
Kaku Y, Kuwata T, Zahid HM, Hashiguchi T, Noda T, Kuramoto N, Biswas S, Matsumoto K, Shimizu M, Kawanami Y, Shimura K, Onishi C, Muramoto Y, Suzuki T, Sasaki J, Nagasaki Y, Minami R, Motozono C, Toyoda M, Takahashi H, Kishi H, Fujii K, Tatsuke T, Ikeda T, Maeda Y, Ueno T, Koyanagi Y, Iwagoe H, Matsushita S.
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Journal Title
Cell Reports
Volume: 36
Issue: 2
Pages: 109385-109385
DOI
Related Report
Peer Reviewed / Open Access
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