Structural basis for the mechanisms of virus entry into host cells

• Project/Area Number: 26713018
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Virology
• Research Institution: Kyushu University
• Principal Investigator: Hashiguchi Takao 九州大学, 医学(系)研究科(研究院), 准教授 (50632098)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥23,920,000 (Direct Cost: ¥18,400,000、Indirect Cost: ¥5,520,000); Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2014: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
• Keywords: 感染症 / ウイルス / 蛋白質 / 構造解析 / 抗体

Outline of Final Research Achievements

To better understand the mechanisms of virus entry, we utilize combined strategies of Structural biology and Virology for mumps virus that causes epidemic parotitis and ebola/marburg virus that cause highly lethal hemorrhagic fever. As the results, we successfully visualized how the viruses enter into host cells at atomic level, which enabled us to better understand a part of the mechanisms of virus entry. These results will illuminate directions toward therapeutics against the viruses.

Research Products

• [Journal Article] Trisaccharide containing alpha2,3-linked sialic acid is a receptor for mumps virus (2016)
  • Author(s): Kubota M, Takeuchi K, Watanabe S, Ohno S, Matsuoka R, Kohda D, Nakakita S, Hiramatsu H, Suzuki Y, Nakayama T, Terada T, Shimizu K, Shimizu N, Shiroishi M, Yanagi Y, Hashiguchi T
  • Journal Title: Proc Natl Acad Sci USA Volume: 113 Issue: 41 Pages: 11579-11584
  • DOI: 10.1073/pnas.1608383113
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Structural Basis for Marburg Virus Neutralization by a Cross-Reactive Human Antibody (2015)
  • Author(s): Hashiguchi T, Fusco ML, Bornholdt ZA, Lee JE, Flyak AI, Matsuoka R, Kohda D, Yanagi Y, Hammel M, Crowe JE, Saphire EO
  • Journal Title: Cell Volume: 160 Issue: 5 Pages: 904-912
  • DOI: 10.1016/j.cell.2015.01.041
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mechanism of human antibody-mediated neutralization of Marburg virus. (2015)
  • Author(s): Flyak AI, Ilinykh PA, Murin CD, Garron T, Shen X, Fusco ML, Hashiguchi T, Bornholdt ZA, Slaughter JC, Sapparapu G, Klages C, Ksiazek TG, Ward AB, Saphire EO, Bukreyev A, and Crowe JE Jr.
  • Journal Title: Cell Volume: 160 Issue: 5 Pages: 893-903
  • DOI: 10.1016/j.cell.2015.01.031
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 糖鎖受容体を介したムンプスウイルス細胞侵入メカニズムの構造生物学的・ウイルス学的解析 (2017)
  • Author(s): 橋口隆生
  • Organizer: 6th Negative Strand Virus-Japan
  • Place of Presentation: 沖縄
• [Presentation] 中和抗体によるエボラ・マールブルグウイルスの侵入阻害機構 (2016)
  • Author(s): 橋口隆生
  • Organizer: 第136回日本薬学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-27
  • Invited
• [Presentation] Inhibitory mechanisms of anti-filovirus antibodies on Marburg and Ebola virus entry (2016)
  • Author(s): Takao Hashguchi
  • Organizer: Institute for Protein Research (IPR) International Seminar IPR / CRED / PDIS Joint Seminar
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2016-01-12
  • Int'l Joint Research / Invited
• [Presentation] 抗体によるエボラ・マールブルグウイルスの中和機構 (2016)
  • Author(s): 橋口隆生、柳雄介、松岡礼、神田大輔、Erica Ollmann Saphire
  • Organizer: 第16回日本蛋白質科学会
  • Place of Presentation: 福岡
• [Presentation] Molecular basis for negative-strand RNA virus entry and neutralization by antibodies. (2016)
  • Author(s): Takao Hashiguchi
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
• [Presentation] Linear saccharide moiety containing α2,3-linked sialic acid, rather than the sialic acid alone, constitutes a receptor for mumps virus (2016)
  • Author(s): Marie Kubota, Kaoru Takeuchi, Shumpei Watanabe, Shinji Ohno, Rei Matsuoka, Daisuke Kohda, Shin-ichi Nakakita, Hiroaki Hiramatsu, Yasuo Suzuki, Tetsuo Nakayama, Tohru Terada, Kentaro Shimizu, Nobutaka Shimizu, Yusuke Yanagi, Takao Hashiguchi.
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
• [Presentation] Tetrameric interaction of the mumps virus hemagglutinin-neuraminidase head domain is critical for triggering membrane fusion. (2016)
  • Author(s): Iori Okabe, Marie Kubota, Shin-ichi Nakakita, Takao Hashiguchi, Yusuke Yanagi.
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
• [Presentation] Characterization of Neutralizing Antibodies against Measles Virus (2016)
  • Author(s): Yoshinari Fukuda, Takao Hashiguchi, Shinji Ohno, Yusuke Yanagi
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
• [Presentation] Structural basis for filovirus neutralization by antibodies (2015)
  • Author(s): Takao Hashguchi
  • Organizer: The 63rd Annual meeting of the Japanese Society for Virology
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2015-11-24
  • Invited
• [Presentation] 抗体によるフィロウイルスの中和の構造基盤 (2015)
  • Author(s): 橋口 隆生
  • Organizer: 感染症国際研究センター/全国共同利用・共同研究拠点 若手ジョイントシンポジウム（東京大学医科学研究所）
  • Place of Presentation: 東京
  • Year and Date: 2015-02-18
  • Invited
• [Presentation] マールブルグウイルス糖蛋白質 GP とヒト由来抗体の X 線結晶構造 (2014)
  • Author(s): 橋口 隆生、柳 雄介、Erica Ollmann Saphire
  • Organizer: 第62回 日本ウイルス学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] モノネガウイルスワクチンの有効性と新規開発の構造基盤 (2014)
  • Author(s): 橋口 隆生
  • Organizer: 「感染・炎症・免疫・発癌」(北海道大学遺伝子病制御研究所)
  • Place of Presentation: 札幌
  • Year and Date: 2014-07-03 – 2014-07-04
  • Invited
• [Book] 医学のあゆみ (2017)
  • Author(s): 久保田万理恵、橋口隆生、柳雄介
  • Total Pages: 6
  • Publisher: 医歯薬出版株式会社
• [Book] 実験医学, 第２章10 抗体医薬研究の最前線と展望 (2015)
  • Author(s): 橋口隆生
  • Total Pages: 220
  • Publisher: 羊土社
• [Book] 進化を続ける構造生物学 (2014)
  • Author(s): 松島 正明, 伊中 浩治, 渡邉 信久, 前仲 勝実, 橋口 隆生, 白石 充典, 中川 敦史, 黒木 良太, 斎藤 稔, 津本 浩平, 樋口 芳樹, 裏出 良博
  • Total Pages: 220
  • Publisher: 化学同人
• [Remarks] Crystal structure of MuV-HN bound to 3-SL
  • URL: http://www.rcsb.org/pdb/explore/explore.do?structureId=5B2D
• [Remarks] Crystal structure of MuV-HN
  • URL: http://www.rcsb.org/pdb/explore/explore.do?structureId=5B2C
• [Remarks] マールブルグウイルス・エボラウイルスの両方に結合する抗体とウイルス糖蛋白質GPの構造
  • URL: http://www.med.kyushu-u.ac.jp/app/modules/information/detail.php?i=759&c=10