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A genome-wide knockout screen identified host factors modulating herpes simplex virus infection

Research Project

Project/Area Number 16H06231
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Virology
Research InstitutionNagoya University

Principal Investigator

SATO Yoshitaka  名古屋大学, 医学系研究科, 助教 (40754940)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
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)
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
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.

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。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (37 results)

All 2019 2018 2017 2016

All Journal Article (13 results) (of which Peer Reviewed: 12 results,  Open Access: 9 results,  Acknowledgement Compliant: 2 results) Presentation (23 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Oncogenesis of CAEBV revealed: Intragenic deletions in the viral genome and leaky expression of lytic genes2019

    • Author(s)
      Murata Takayuki、Okuno Yusuke、Sato Yoshitaka、Watanabe Takahiro、Kimura Hiroshi
    • Journal Title

      Reviews in Medical Virology

      Volume: 30 Issue: 2

    • DOI

      10.1002/rmv.2095

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oncolytic activity of HF10 in head and neck squamous cell carcinomas2019

    • Author(s)
      Esaki Shinichi、Goshima Fumi、Ozaki Haruka、Takano Gaku、Hatano Yoshimi、Kawakita Daisuke、Ijichi Kei、Watanabe Takahiro、Sato Yoshitaka、Murata Takayuki、Iwata Hiromitsu、Shibamoto Yuta、Murakami Shingo、Nishiyama Yukihiro、Kimura Hiroshi
    • Journal Title

      Cancer Gene Therapy

      Volume: - Issue: 7-8 Pages: 585-598

    • DOI

      10.1038/s41417-019-0129-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] S-Like-Phase Cyclin-Dependent Kinases Stabilize the Epstein-Barr Virus BDLF4 Protein To Temporally Control Late Gene Transcription2019

    • Author(s)
      Sato Yoshitaka、Watanabe Takahiro、Suzuki Chihiro、Abe Yuichi、Masud H. M. Abdullah Al、Inagaki Tomoki、Yoshida Masahiro、Suzuki Takeshi、Goshima Fumi、Adachi Jun、Tomonaga Takeshi、Murata Takayuki、Kimura Hiroshi
    • Journal Title

      Journal of Virology

      Volume: 93 Issue: 8

    • DOI

      10.1128/jvi.01707-18

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antitumor activity of cyclin‐dependent kinase inhibitor alsterpaullone in Epstein‐Barr virus‐associated lymphoproliferative disorders2019

    • Author(s)
      Watanabe Takahiro、Sato Yoshitaka、Masud H. M. Abdullah Al、Takayama Masahiro、Matsuda Hiroki、Hara Yuya、Yanagi Yusuke、Yoshida Masahiro、Goshima Fumi、Murata Takayuki、Kimura Hiroshi
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 1 Pages: 279-287

    • DOI

      10.1111/cas.14241

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Challenges in Managing EBV-Associated T- and NK-Cell Lymphoproliferative Diseases2018

    • Author(s)
      Sato Yoshitaka
    • Journal Title

      Frontiers in Pediatrics

      Volume: 6

    • DOI

      10.3389/fped.2018.00320

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antitumor effects of duvelisib on Epstein-Barr virus-associated lymphoma cells2018

    • Author(s)
      Kawada, J. Ando, S. Torii, Y. Watanabe, T. Sato, Y. Ito, Y. Kimura, H.
    • Journal Title

      Cancer Med

      Volume: 印刷中 Issue: 4 Pages: 1275-1284

    • DOI

      10.1002/cam4.1311

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elimination of LMP1-expressing cells from a monolayer of gastric cancer AGS cells.2017

    • Author(s)
      Sato Y, Ochiai S, Murata T, Kanda T, Goshima F, Kimura H.
    • Journal Title

      Oncotarget

      Volume: 印刷中 Issue: 24 Pages: 39345-39355

    • DOI

      10.18632/oncotarget.16996

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Epstein-Barr Virus BRRF1 Gene Is Dispensable for Viral Replication in HEK293 cells and Transformation2017

    • Author(s)
      Yoshida Masahiro、Watanabe Takahiro、Narita Yohei、Sato Yoshitaka、Goshima Fumi、Kimura Hiroshi、Murata Takayuki
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 6044-6044

    • DOI

      10.1038/s41598-017-06413-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epstein-Barr Virus BKRF4 Gene Product Is Required for Efficient Progeny Production.2017

    • Author(s)
      H. M. Abdullah Al Masud、Takahiro Watanabe、 Masahiro Yoshida、 Yoshitaka Sato、 Fumi Goshima、 Hiroshi Kimura、 Takayuki Murata
    • Journal Title

      Journal of Virology

      Volume: 91 Issue: 23

    • DOI

      10.1128/jvi.00975-17

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of a Suppressive Cis-acting Element in the Epstein?Barr Virus LMP1 Promoter2017

    • Author(s)
      Yoshida Masahiro、Murata Takayuki、Ashio Keiji、Narita Yohei、Watanabe Takahiro、Masud H. M. Abdullah Al、Sato Yoshitaka、Goshima Fumi、Kimura Hiroshi
    • Journal Title

      Frontiers in Microbiology

      Volume: 8 Pages: 2302-2302

    • DOI

      10.3389/fmicb.2017.02302

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The efficacy of combination therapy with oncolytic herpes simplex virus HF10 and dacarbazine in a mouse melanoma model2017

    • Author(s)
      Rui Tanaka、Fumi Goshima、Shinichi Esaki、Yoshitaka Sato、Takayuki Murata、Yukihiro Nishiyama、Daisuke Watanabe、Hiroshi Kimura
    • Journal Title

      American Journal of Cancer Research

      Volume: 7 Pages: 1693-1703

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Elimination of LMP1-expressing cells from a monolayer of gastric cancer AGS cells2017

    • Author(s)
      Yoshitaka Sato, Shingo Ochiai, Takayuki Murata, Teru Kanda, Fumi Goshima, and Hiroshi Kimura
    • Journal Title

      Oncotarget

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The C-terminus of Epstein-Barr virus BRRF2 is required for its proper localization and efficient virus production2017

    • Author(s)
      Takahiro Watanabe, Keiya Sakaida, Masahiro Yoshida, H. M. Abdullah Al Masud, Yoshitaka Sato, Fumi Goshima, Hiroshi Kimura, and Takayuki Murata
    • Journal Title

      Frontiers in Microbiology

      Volume: 8 Pages: 125-125

    • DOI

      10.3389/fmicb.2017.00125

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Genome analysis of chronic active Epstein-Barr virus infection2019

    • Author(s)
      Takayuki Murata, Yusuke Okuno, Yoshitaka Sato, Takahiro Watanabe, Hiroshi Kimura
    • Organizer
      The 18th Awaji International Forum on Infection and Immunity
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dynamic changes in the cellular environment during Epstein-Barr virus productive replication2019

    • Author(s)
      佐藤好隆
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Exosomal transfer of viral proteins enhances Epstein-Barr virus infection2019

    • Author(s)
      佐藤好隆、村田貴之、五島典、渡辺崇広、木村宏
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Stress conditions promote cell-free infection of Epstein-Barr virus2019

    • Author(s)
      高木舜晟、佐藤好隆、佐藤佳、木村宏、岩見真吾
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Identifying host factors for HSV ionfection by genome-wide CRISPR screen2019

    • Author(s)
      鈴木健史、佐藤好隆、奥野友介、五島典、村田貴之、渡辺崇広、木村宏
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ウイルス感染細胞から放出される内因性微粒子によるウイルス感染の促進2019

    • Author(s)
      矢口正宏、佐藤好隆、村田貴之、渡辺崇広、五島典、木村宏
    • Organizer
      第16回EBウイルス研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] CRISPR screenを用いたHSV-1感染に必要な宿主因子の網羅的解析2019

    • Author(s)
      鈴木健史、佐藤好隆、奥野友介、渡辺崇広、五島典、木村宏
    • Organizer
      第33回ヘルペスウイルス研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Epstein-Barrウイルスの再活性化に関わる分子基盤に迫るCRISPRスクリーニング2019

    • Author(s)
      佐藤好隆、稲垣知希、奥野友介、鈴木健史、村田貴之、H. M. Abdullah Al Masud、渡辺崇広、五島典、木村宏
    • Organizer
      第33回ヘルペスウイルス研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ウイルス遺伝子発現制御機構に基づいた抗Epstein-Barrウイルス薬の探索2019

    • Author(s)
      佐藤好隆、渡辺崇広、木村宏
    • Organizer
      第60回臨床ウイルス学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] CDK2 complexes stabilize the Epstein-Barr virus BDLF4 protein to temporally control late gene transcription2018

    • Author(s)
      佐藤好隆、渡辺崇広、鈴木ちひろ、阿部雄一、H.M. Abdullah Al Masud、五島典、村田貴之、木村宏
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] CDK2複合体によるEBVBDLF4タンパク質のリン酸化を介したウイルス後期遺伝子発現制御機構の解析2018

    • Author(s)
      佐藤好隆、渡辺崇広、鈴木ちひろ、阿部雄一、五島典、村田貴之、木村宏
    • Organizer
      第32回ヘルペスウイルス研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] S-phase CDKs Stabilize the Epstein-Barr Virus BDLF4 Protein to Temporally Control Late Gene Transcription2018

    • Author(s)
      Takahiro Watanabe, Yoshitaka Sato, Chihiro Suzuki, Yuichi Abe, Fumi Goshima, Takayuki Murata, Hiroshi Kimura
    • Organizer
      2018 International Conference on EBV & KSHV
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CDK阻害剤はEBV遺伝子の発現を抑制することで抗EBV活性を示す2018

    • Author(s)
      佐藤好隆、渡辺崇広、鈴木ちひろ、五島典、村田貴之、木村宏
    • Organizer
      第27回EBウイルス感染症研究会
    • Related Report
      2017 Annual Research Report
  • [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
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The C-Terminus of Epstein-Barr Virus BRRF2 Is Required for its Proper Localization and Efficient Virus Production2017

    • Author(s)
      Takahiro Watanabe, Masahiro Yoshida, H.M. Abdullah Al Masud, Yoshitaka Sato, Fumi Goshima, Hiroshi Kimura, Takayuki Murata
    • Organizer
      The 42nd Annual International Herpesvirus Workshop (IHW2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] IL-8/EGFRシグナルの活性化を介したLMP1発現細胞と非発現細胞の細胞競合2017

    • Author(s)
      佐藤好隆、落合伸伍、神田 輝、村田貴之、五島典、木村宏
    • Organizer
      第14回EBウイルス研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ell competition between LMP1-positive and -negative gastric cancer AGS cells2017

    • Author(s)
      Yoshitaka Sato、Shingo Ochiai、Takayuki Murata、Teru Kanda、Fumi Goshima、Hiroshi Kimura
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] HSV病原性発現機構に関わる宿主因子の網羅的検索2017

    • Author(s)
      佐藤好隆、奥野友介、吉田全宏、五島典、村田貴之、木村
    • Organizer
      第31回ヘルペスウイルス研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] EBV 後期遺伝子転写を阻害する小分子化合物の探索2016

    • Author(s)
      佐藤好隆、中切健太、五島典、村田貴之、木村宏
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Comprehensive genetic study of chronic active EBV infection2016

    • Author(s)
      Takayuki Murata, Yusuke Okuno, Yoshinori Ito, Yoshitaka Sato, Seiji Kojima, Seishi Ogawa, Hiroshi Kimura
    • Organizer
      The 17th International Symposium on EBV and associated diseases (EBV2016)
    • Place of Presentation
      チューリッヒ(スイス)
    • Year and Date
      2016-08-08
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibition of LMP1-driven growth promotion in AGS gastric epithelial cells by co-culture with LMP1-negative cells2016

    • Author(s)
      Yoshitaka Sato, Takayuki Murata, Teru Kanda, Shingo Ochiai, Fumi Goshima, Hiroshi Kimura
    • Organizer
      The 17th International Symposium on EBV and associated diseases (EBV2016)
    • Place of Presentation
      チューリッヒ(スイス)
    • Year and Date
      2016-08-08
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 胃癌細胞集団から EBV LMP1 発現細胞は排除される2016

    • Author(s)
      佐藤好隆、落合伸伍、神田 輝、村田貴之、五島典、木村宏
    • Organizer
      第30回ヘルペスウイルス研究会
    • Place of Presentation
      クロス・ウエーブ府中(東京都府中市)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] EBV LMP1タンパク質発現細胞と非発現細胞間の細胞競合2016

    • Author(s)
      佐藤好隆、落合伸伍、神田 輝、村田貴之、五島典、木村宏
    • Organizer
      第13回EBウイルス研究会
    • Place of Presentation
      東京医科歯科大学(東京都文京区)
    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] 抗ウイルス薬2017

    • Inventor(s)
      佐藤好隆、渡辺崇広、木村宏
    • Industrial Property Rights Holder
      名古屋大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-250093
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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