Study for entry receptor of emerging hemorrhagic fever virus and its application for antivirals

• Project/Area Number: 15K08510
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: University of Toyama (2016-2017); National Institute of Infectious Diseases (2015)
• Principal Investigator: TANI HIDEKI 富山大学, 大学院医学薬学研究部(医学), 准教授 (20397706)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 新興ウイルス感染症 / SFTSV / 細胞侵入 / Entry signaling / SFTSV-GP / Cell-to-cell fusion / アミノ酸変異 / リポーターアッセイ / LAMP-1 / 細胞融合

Outline of Final Research Achievements

Because hemorrhagic fever virus infection has a high fatality rate and causes severe disease, it is important to prevent virus infection itself, and it is urgent to elucidate the mechanism of adsorption and invasion in the early stage of infection. In this study, we analyzed the properties of the novel entry receptor, lysosome-associated membrane protein 1, for Lassa virus and the viral envelope proteins and host factors for severe fever with thrombocytopenia syndrome virus (SFTSV). As a result, it was possible to identify amino acids of envelope proteins involved in cell fusion of SFTSV. In addition, signal molecules activated upon cell entry could also be identified as a host factor.

Research Products

• [Journal Article] A neutralization assay with a severe fever with thrombocytopenia syndrome virus strain that makes plaques in inoculated cells. (2017)
  • Author(s): Taniguchi S, Fukuma A, Tani H, Fukushi S, Saijo M, Shimojima M.
  • Journal Title: J Virol Methods. Volume: 244 Pages: 4-10
  • DOI: 10.1016/j.jviromet.2017.01.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 重症熱性血小板減少症候群の抗ウイルス療法―ファビピラビルとリバビリン― (2017)
  • Author(s): 西條政幸、谷 英樹
  • Journal Title: 化学療法の領域 Volume: 33 Pages: 97-103
• [Journal Article] Characterization of severe fever with thrombocytopenia syndrome virus glycoprotein-mediated entry. (2016)
  • Author(s): Tani H, Shimojima M, Fukushi S, Yoshikawa T, Fukuma A, Taniguchi S, Morikawa S, Saijo M.
  • Journal Title: J Virol. Volume: 90 Issue: 11 Pages: 5292-301
  • DOI: 10.1128/jvi.00110-16
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 抗SFTSウイルス薬開発の進捗状況 (2016)
  • Author(s): 谷 英樹
  • Journal Title: Infectious Agents Surveillance Report (IASR) Volume: 37 Pages: 49-50
  • Peer Reviewed / Open Access
• [Presentation] Identification of amino acid residue important for fusion of the glycoprotein of severe fever with thrombocytopenia syndrome virus (2018)
  • Author(s): Hideki Tani, Kengo Kawachi, Masayuki Shimojima, Shuetsu Fukushi, Takeshi Kurosu, Shigeru Morikawa, Masayuki Saijo
  • Organizer: 20th International Conference on Emerging Infectious Diseases (EID). 50th Joint Working Conference on Viral Diseases
• [Presentation] The protein kinase inhibitors inhibit entry of severe fever with thrombocytopenia syndrome virus in vitro (2017)
  • Author(s): Hideki Tani, Hikaru Fujii, Satoshi Taniguchi, Shuetsu Fukushi, Takeshi Kurosu, Masayuki Shimojima, Shigeru Morikawa, Masayuki Saijo
  • Organizer: The 65th annual meeting of the Japanese society for virology
• [Presentation] Determination of the amino acid residue important for fusion of severe fever with thrombocytopenia syndrome virus glycoprotein (2016)
  • Author(s): Kengo Kawachi, Hideki Tani, Masayuki Shimojima, Shuetsu Fukushi, Takeshi Kurosu, Wataru Kamitani, Masayuki Saijo
  • Organizer: The 64th annual meeting of the Japanese society for virology
  • Place of Presentation: Sapporo Convention Center
  • Year and Date: 2016-10-23