Comprehensive analysis of post-translational modification of herpesvirus based on big data analysis using supercomputer

• Project/Area Number: 19K22524
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: KAWAGUCHI Yasushi 東京大学, 医科学研究所, 教授 (60292984)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: HSV / 蛋白質翻訳後修飾 / MDシミュレーション / スパコン / シミュレーション / 抵抗性因子

Outline of Research at the Start

近年、質量解析計の飛躍的な進歩により、蛋白質翻訳後修飾に関するビッグデータの取得が可能となりつつある。しかしながら、各翻訳後修飾の生物学的意義の解明には、依然として莫大な労力を要するため、ごく一部の限定的な翻訳後修飾のみが解析されている。したがって、本研究では「高度計算処理機を駆使し膨大な翻訳後修飾情報を収集し、科学的根拠に基づき機能的な修飾情報を客観的に抽出する」という基盤技術の創成を試みる。本研究により確立されるビックデータ解析プラットフォームは、ウイルス学のみならず、生物学研究全体の発展にも直結することが期待される。

Outline of Final Research Achievements

We have comprehensively identified post-translational modifications (PTM) of the proteins encoded by herpes simplex virus (HSV). Among the HSV proteins, PTM of the proteins responsible for HSV functional regulations were identified by molecular dynamics (MD) simulation. It was suggested that PTM is responsible reducing the motility of the functional domain of HSV proteins.

Academic Significance and Societal Importance of the Research Achievements

HSV生活環を司る感染特異的な翻訳後修飾は、理想的な抗HSV剤の創薬標的となりうることから、本技術基盤の創成および各HSV蛋白質の翻訳後修飾の意義の解明は重要な研究課題であると考えられる。

Research Products

• [Journal Article] Role of the orphan transporter SLC35E1 in the nuclear egress of herpes simplex virus 1 (2022)
  • Author(s): Fumio Maeda, Akihisa Kato, Kosuke Takeshima, Misato Shibazaki, Ryota Sato, Takuma Shibata, Kensuke Miyake, Hiroko Kozuka-Hata, Masaaki Oyama, Eigo Shimizu, Seiya Imoto, Satoru Miyano, Shungo Adachi, Tohru Natsume, Koh Takeuchi, Yuhei Maruzuru, Naoto Koyanagi, Jun Arii, Yasushi Kawaguchi
  • Journal Title: Journal of Virology Volume: - Issue: 10 Pages: 10-10
  • DOI: 10.1128/jvi.00306-22
  • Peer Reviewed / Open Access
• [Journal Article] Identification of a herpes simplex virus 1 gene encoding neurovirulence factor by chemical proteomics (2020)
  • Author(s): Kato Akihisa、Adachi Shungo、Kawano Shuichi、Takeshima Kousuke、Watanabe Mizuki、Kitazume Shinobu、Sato Ryota、Kusano Hideo、Koyanagi Naoto、Maruzuru Yuhei、Arii Jun、Hatta Tomohisa、Natsume Tohru、Kawaguchi Yasushi
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 4894-4894
  • DOI: 10.1038/s41467-020-18718-9
  • Peer Reviewed / Open Access
• [Journal Article] Phosphoregulation of a Conserved Herpesvirus Tegument Protein by a Virally Encoded Protein Kinase in Viral Pathogenicity and Potential Linkage between Its Evolution and Viral Phylogeny (2020)
  • Author(s): Shibazaki Misato、Kato Akihisa、Takeshima Kosuke、Ito Jumpei、Suganami Mai、Koyanagi Naoto、Maruzuru Yuhei、Sato Kei、Kawaguchi Yasushi
  • Journal Title: Journal of Virology Volume: 94 Issue: 18 Pages: 1-4
  • DOI: 10.1128/jvi.01055-20
  • Peer Reviewed / Open Access
• [Journal Article] Identification of the Capsid Binding Site in the Herpes Simplex Virus 1 Nuclear Egress Complex and Its Role in Viral Primary Envelopment and Replication. (2019)
  • Author(s): Takeshima K, Arii J, Maruzuru Y, Koyanagi N, Kato A, Kawaguchi Y.
  • Journal Title: J Virol. Volume: 93 Issue: 21
  • DOI: 10.1128/jvi.01290-19
  • Peer Reviewed / Open Access
• [Journal Article] A role for the CCR5?CCL5 interaction in the preferential migration of HSV-2-specific effector cells to the vaginal mucosa upon nasal immunization (2019)
  • Author(s): Joo Sunyi、Suwanto Aldina、Sato Ayuko、Nakahashi-Ouchida Rika、Mori Hiromi、Uchida Yohei、Sato Shintaro、Kurashima Yosuke、Yuki Yoshikazu、Fujihashi Kohtaro、Kawaguchi Yasushi、Kiyono Hiroshi
  • Journal Title: Mucosal Immunology Volume: 12 Issue: 6 Pages: 1391-1403
  • DOI: 10.1038/s41385-019-0203-z
  • Peer Reviewed / Open Access
• [Journal Article] Roles of the Interhexamer Contact Site for Hexagonal Lattice Formation of the Herpes Simplex Virus 1 Nuclear Egress Complex in Viral Primary Envelopment and Replication. (2019)
  • Author(s): Arii J, Takeshima K, Maruzuru Y, Koyanagi N, Kato A, Kawaguchi Y.
  • Journal Title: J Virol. Volume: 93 Issue: 14
  • DOI: 10.1128/jvi.00498-19
  • Peer Reviewed / Open Access
• [Presentation] Molecular Mechanisms of Herpes Simplex Virus Infection (2021)
  • Author(s): Yasushi Kawaguchi
  • Organizer: 第19回あわじ感染と免疫国際フォーラム / The Neo-Virology Symposium
  • Int'l Joint Research / Invited
• [Presentation] 単純ヘルペスウイルス感染の分子機構 (2020)
  • Author(s): 川口 寧
  • Organizer: 第50回日本皮膚免疫アレルギー学会総会学術大会
  • Invited
• [Presentation] HSV UL13 プロテインキナーゼの新規キナーゼ活性制御機構の解明 (2019)
  • Author(s): 小栁直人, 加藤哲久, 丸鶴雄平, 有井潤, 川口寧
  • Organizer: 第33回ヘルペスウイルス研究会
• [Presentation] HSV-1 Us3 protein kinaseの基質特異性を司るリン酸化制御機構の解明 (2019)
  • Author(s): 木村南美, 加藤哲久，五十嵐学, 丸鶴雄平，小栁直人，有井潤，川口寧
  • Organizer: 第33回ヘルペスウイルス研究会
• [Presentation] Regulatory mechanism of the substrate specificity of Us3 protein kinase encoded by herpes simplex virus-1 (2019)
  • Author(s): Akihisa Kato, Nami Kimura, Naoto Koyanagi, Yuhei Maruzuru, Jun Arii, Manabu Igarashi, Yasushi Kawaguchi
  • Organizer: 第67回日本ウイルス学会学術集会
• [Presentation] 単純ヘルペスウイルスの増殖・病態発現機構 (2019)
  • Author(s): 川口 寧
  • Organizer: 第33回ヘルペスウイルス研究会
  • Invited
• [Remarks] 東京大学医科学研究所 感染・免疫部門 ウイルス病態制御分野
  • URL: http://www.ims.u-tokyo.ac.jp/Kawaguchi-lab/KawaguchiLabTop.html