The involvement of amino acid mutations of the capsid ptoteins of enterovirus A71 in viral genetic diversity and neuropathogenesis
Project/Area Number |
16H05200
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Virology
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Research Institution | National Institute of Infectious Diseases |
Principal Investigator |
Shimizu Hiroyuki 国立感染症研究所, ウイルス第二部, 室長 (90270644)
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Project Period (FY) |
2016-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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Keywords | エンテロウイルス / エンテロウイルスA71 / 病原性 / 動物モデル / 受容体 / PSGL-1 / 手足口病 / エンテロウイルス71 / ウイルス / 感染症 |
Outline of Final Research Achievements |
The development of a novel animal model exhibiting similar receptor specificities in humans is critical to elucidate the mechanism of neuropathogenicity due to EV-A71 infection. In a cynomolgus model, infection with the PSGL-1-binding EV-A71 strain (VP1-145Q) did not induce apparent virus replication and pathogenesis. We then established knock-in mice expressing several human EV-A71 receptors and investigated viral replication and pathogenicity in the mice infected with various EV-A71 strains. However, any viral replication and clinical symptoms were not observed. In this study, we failed to develop an animal model for the PSGL-1-dependent replication and pathogenicity but gained valuable insights to improving animal models for analyzing human receptor specificities against EV-A71.
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Academic Significance and Societal Importance of the Research Achievements |
EV-A71感染における重症中枢神経疾患の発症機構は明らかにされておらず、ヒトにおける重篤化を規定するウイルス側・宿主側因子は特定されていない。ヒトにおける受容体特性を反映した動物モデルの開発により、EV-A71感染による神経病原性発現機構の解明が期待できる。本研究では、PSGL-1受容体を介するウイルス増殖・病原性発現を反映した動物感染モデルを開発することは出来なかったが、ヒト受容体特性を解析するための動物モデルの改良に資する研究成果が得られた。ヘパラン硫酸、SCARB2等、PSGL-1以外の受容体の関与も踏まえた今後の検討が必要とされる。
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Report
(5 results)
Research Products
(47 results)
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[Journal Article] A novel combination therapy for human oxaliplatin-resistant colorectal cancer using oxaliplatin and coxsackievirus A11.2018
Author(s)
Wang, B., Ogata, H., Takishima, Y., Miyamoto, S., Inoue, H., Kuroda, M., Yamada, K., Hijikata, Y., Murahashi, M., Shimizu, H., Okazaki, T., Nakanishi, Y., Tani, K.
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Journal Title
Anticancer Res.
Volume: 38
Issue: 11
Pages: 6121-6126
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] VP1 amino acid residue 145 of enterovirus 71 is a key residue for its receptor attachment and resistance to neutralizing antibody during cynomolgus monkey infection2018
Author(s)
Fujii K, Sudaka Y, Takashino A, Kobayashi K, Kataoka C, Suzuki T, Iwata-Yoshikawa N, Kotani O, Ami Y, Shimizu H, Nagata N, Mizuta K, Matsuzaki Y, Koike S.
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Acute Flaccid Myelitis Collaborative Study I. Clinical Features of Acute Flaccid Myelitis Temporally Associated With an Enterovirus D68 Outbreak: Results of a Nationwide Survey of Acute Flaccid Paralysis in Japan, August-December 20152018
Author(s)
Chong PF, Kira R, Mori H, Okumura A, Torisu H, Yasumoto S, Shimizu H, Fujimoto T, Hanaoka N, Kusunoki S, Takahashi T, Oishi K, Tanaka-Taya K
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Journal Title
Clin Infect Dis
Volume: 66
Issue: 5
Pages: 653-664
DOI
Related Report
Peer Reviewed
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[Journal Article] Neuropathogenicity of Two Saffold Virus Type 3 Isolates in Mouse Models.2016
Author(s)
Kotani O, Naeem A, Suzuki T, Iwata-Yoshikawa N, Sato Y, Nakajima N, Hosomi T, Tsukagoshi H, Kozawa K, Hasegawa H, Taguchi F, Shimizu H, Nagata N.
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Journal Title
PLOS One
Volume: 11
Issue: 2
Pages: 1-29
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Outbreak of type 1 vaccine-derived poliovirus in Lao People's Democratic Republic in 2015-20162016
Author(s)
Shimizu H, Vongphrachanh P, Khamphaphongphane B, Sengkeopraseuth B, Nakamura T, Nishimura Y, Arita M, Wada J, Yoshida H, Schluter WW, Datta SS
Organizer
Europic 2016
Place of Presentation
Switzerland
Year and Date
2016-09-04
Related Report
Int'l Joint Research
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[Presentation] he VP1 amino acid residue 145 of EV71 is a virulence determinant in SCARB2-dependent infection2016
Author(s)
Fujii K, Sudaka Y, Ayumi Imura, Takashino A, Kataoka C, Suzuki T, Iwata-Yoshikawa N, Kotani O, Ami Y, Shimizu H, Nagata N, Koike K
Organizer
Europic 2016
Place of Presentation
Switzerland
Year and Date
2016-09-04
Related Report
Int'l Joint Research
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