| Project/Area Number |
18K17362
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 58020:Hygiene and public health-related: including laboratory approach
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| Research Institution | Fujita Health University (2019)
Kyoto Pharmaceutical University (2018) |
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Principal Investigator |
Abe Atsuko 藤田医科大学, その他部局等, 日本学術振興会特別研究員(PD) (70780774)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | カポジ肉腫関連ヘルペスウイルス / ユビキチン様タンパク質 / FAT10 / ヘルペスウイルス / KSHV / ウイルス粒子形成 |
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| Outline of Final Research Achievements |
After primary infection, KSHV persists lifelong as a chronic asymptomatic infection in its human host but establishes latency. Productive infection, which occurs spontaneously or can be induced artificially, lead to virus production. It is well established that herpesviruses hijack host machineries for their lytic replication but little is known which factors are involved in KSHV. Here, we performed proteomic analysis with KSHV lytic replication-induced cells to explore a new mechanism of KSHV lytic replication. E1 activating enzyme Ubiquitin-like modifier activating enzyme 6 (UBA6 or UBE1L2), which activates both ubiquitin and FAT10, were identified by proteome analysis. Knockout of UBE1L2 reduced KSHV viral productions. We also explored target proteins of FAT10ylation by immunoprecipitation-MS using FAT10 specific antibody and some viral proteins were identified. Our results suggested UBE1L2 is involved in KSHV viral productions by FAT10ylation of some viral proteins.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の目的は、KSHV溶解感染に中心的に働くUBLの同定とその溶解感染に果たす詳細な役割を明らかにすることである。これまでUBLとヘルペスウイルスの関連は全く指摘されておらず、今回申請者が指摘しているのが世界初となる。本研究では、スクリーニングに網羅的プロテオーム解析を用いている。KSHVは約90種類のタンパク質をコードしており、複雑な生活環をもつウイルスであるため、従来の方法とは異なる効率的なスクリーニング系が必要となってくる。ヘルペスウイルスの溶解感染機構は共通している部分も多く、本研究を応用することで他のヘルペスウイルスの溶解感染機構の研究も発展させることができると考えている。
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