| Project/Area Number |
16K08362
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Environmental and hygienic pharmacy
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
Saito Kyoko 国立感染症研究所, 細胞化学部, 主任研究官 (70235034)
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| Project Period (FY) |
2016-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | フラビウイルス / コレステロール / 脂質 / ゲノム複製 / レプリコン / 黄熱ウイルス / Vero細胞 / ウイルス / 感染症 |
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| Outline of Final Research Achievements |
The genus Flavivirus in the family Flaviviridae includes many viruses that cause arthropod-borne infectious diseases. Currently, no effective antiviral agents have been developed against flaviviruses. The aim of this study was to analyze the importance of host cell lipids such as cholesterol in the replication of flaviviruses. First, a subgenomic replicon based on yellow fever virus strain 17D, a type of flavivirus, was generated and then Vero cell lines in which the replicon continuously replicates were established. Using the replicon cells and a cultured cell-based infection system, it was found that one of the cholesterol synthesis inhibitors inhibited the genome replication of yellow fever virus strain 17D. The target of the inhibitor will be closely examined and its potential as an antiviral agent will be evaluated in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
樹立したレプリコン細胞は抗ウイルス剤の探索の他、宿主因子の遺伝学的探索にも利用可能であり、宿主因子を標的とした抗フラビウイルス戦略の研究にも有用であると考えられる。また、レプリコン細胞はウイルス感染細胞におけるゲノム複製過程をミミックしているので、その分子メカニズムの解析にも役立つ。本研究で見出したコレステロール合成阻害剤の一つは、黄熱ウイルス17D株の一過的な複製に加えて持続化した複製に対する抑制効果が高く、抗ウイルス剤候補として有望であると考えられる。
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