A genome-wide knockout screen identified host factors modulating herpes simplex virus infection
| Project/Area Number |
16H06231
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | Nagoya University |
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Principal Investigator |
SATO Yoshitaka 名古屋大学, 医学系研究科, 助教 (40754940)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥25,220,000 (Direct Cost: ¥19,400,000、Indirect Cost: ¥5,820,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2016: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
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| Keywords | 単純ヘルペスウイルス / CRISPRスクリーニング / HSV-1 / HSV-2 / ハプロイド細胞 / ハプロイドスクリーニング / 宿主因子 / ウイルス感染 / HSV / スクリーニング / ウイルス / 感染症 / ウィルス |
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| Outline of Final Research Achievements |
Herpes simplex virus (HSV) is a common pathogen that causes skin infection as well as fatal encephalitis. HSV is categorized into 2 types: HSV type 1 (HSV-1) and HSV type 2 (HSV-2). Targeting host factors involved in HSV-infection and -propagation is an attractive approach to regulate those viruses. To identify a set of HSV host factors, we carried out a genome wide CRISPR screen. In this study, we established high quality KO library that showed the presentation of over 98% individual sgRNA. We isolated 53 genes for HSV-1, and 21 genes for HSV-2 as responsible host genes for viral infection and propagation. Among these isolated genes, NECTIN-1 and a series of genes involved in heparan sulfate biosynthesis, which are known for HSV viral receptors, were included. The other candidate genes are currently being investigated. Our study may provide new insights into the molecular mechanism of HSV viral entry and of the tropism that differs between HSV-1 and HSV-2.
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| Academic Significance and Societal Importance of the Research Achievements |
人類は常にウイルス感染に晒されている。病原性のないものから致死的なものまで様々なヒトに感染するウイルスが存在するが、抗ウイルス薬が未だ存在しないウイルスがほとんどである。ウイルスは自身単独では増殖出来ず、必ず宿主が必要になる。従って、ウイルスが利用する宿主因子は治療標的となり、ウイルスが利用する宿主因子の同定およびその分子基盤の解明は、抗ウイルス薬の開発に大きく貢献できる。本研究では、ヒトに脳炎などをきたす単純ヘルペスウイルス1型 (Herpes simplex virus type-1:HSV-1) が利用する宿主因子の網羅的解析を行い、既知の因子を含む53の宿主因子候補遺伝子を同定した。
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Report
(5 results)
Research Products
(37 results)
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[Presentation] Genetic Background of Chronic Active Epstein-Barr Virus Disease2017
Author(s)
Yusuke Okuno, Takayuki Murata, Yoshitaka Sato, Hideki Muramatsu, Norihiro Murakami, Tatsuya Okuno, Kenichi Yoshida, Yoshinori Ito, Akihisa Sawada, Koichi Ohshima, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Yoshiyuki Takahashi, Seiji Kojima, Seishi Ogawa, and Hiroshi Kimura
Organizer
American Society of Hematology 59th Annual Meeting and Exposition
Related Report
Int'l Joint Research
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