| Project/Area Number |
16K15281
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Virology
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| Research Institution | National Institute of Infectious Diseases (2017-2018)
Kanazawa University (2016) |
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Principal Investigator |
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| Research Collaborator |
Wakae Kousho
Que Lusheng
Li YingFang
Kitamura Koichi
田島 敦
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | ヒトポリオーマウイルス / viral DNA integration / ウイルス発がん / APOBEC3 / ポリオーマウイルス / ゲノム挿入 / 発ガン / 変異 / ポロオーマウイルス / virus / cancer / genome integration / Polyomavirus / ウイルス / ゲノム / 発癌 |
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| Outline of Final Research Achievements |
Recently, Merkel polyomavirus (MCV) has been reported to cause Merkel cell carcinoma. Viral DNA integration is one of the prominent molecular characteristics of MCV-derived tumorigenesis. Therefore, elucidation of the mechanism of viral DNA integration is very important to understand Merkel cell carcinoma. However, the lack of cellular model of viral DNA integration hampers the study of viral DNA integration. To develop a new cellular model of MCV viral DNA integration, we made a recombinant MCV virus that retains a drug-resistant gene. When we infected cells with the recombinant virus and cultivated the infectants in the presence of puromycin, drug-resistant infectants were obtained. Importantly, these infectants retained not only episomal viral DNA but also integrated DNA, which was detected by Southern blot hybridization. This recombinant MCV infection system may be useful for the study of MCV viral DNA integration.
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| Academic Significance and Societal Importance of the Research Achievements |
ポリオーマウイルスやパピローマウイルスの宿主ゲノムへのゲノム挿入現象は、発がんの中心的機構であると理解されていたが、それを培養細胞で観察する実験系がないため、研究が滞っていた。本研究では、薬剤耐性遺伝子を持つポリオーマウイルスを作成し、薬剤選別を行うことで、培養細胞でゲノム挿入現象を観察できる系を構築した。構築された細胞系を使うことで、今後ゲノム挿入を規定するウイルス側因子や宿主側因子を同定できる可能性が開け、それらを丹念に決定して行くことで、どのような時にゲノム挿入が起こるか、どのようにそれを防ぐのかといった発がんの予知や予防法の開発研究の可能性が開けた。
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