| Project/Area Number |
25860832
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Infectious disease medicine
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
KATAOKA Chikako 国立感染症研究所, その他部局等, 研究員 (10646623)
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| Research Collaborator |
SHIMIZU Hiroyuki
NISHIMURA Yorihiro
WAKITA Takaji
AMI Yasushi
NAGATA Noriyo
SUZUKI Tadaki
IWATA Naoko (YOSHIKAWA Naoko)
KOTANI Osamu
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | エンテロウイルス / 感染動物モデル / 選択圧 / ウイルス学 / 病原性 / ウイルス感染 / 動物モデル / 神経ウイルス |
|---|
| Outline of Final Research Achievements |
We identified PSGL-1 as an EV71 receptor before.In this study, we investigated viral replication, genetic stability, and the pathogenicity of PSGL-1-binding (PB with VP1-145G) and PSGL-1-nonbinding (non-PB with VP1-145E) strains of EV71 in a cynomolgus monkey model. Mild neurological symptoms, transient lymphocytopenia, and inflammatory cytokine responses were found predominantly in the non-PB-inoculated monkeys. After inoculation with EV71, almost all EV71 detected in clinical samples, central nervous system (CNS), and non-CNS tissues of both inoculated groups, possessed VP1-145E, suggesting a strong in vivo selection of VP1-145E variants and CNS spread presumably in a PSGL-1-independent manner. Thus, VP1-145E variants are mainly responsible for the development of viremia and neuropathogenesis in a non-human primate model, further suggesting the in vivo involvement of amino acid polymorphism at VP1-145 in cell-specific viral replication and pathogenesis in EV71-infected individuals.
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