Establishment of reverse genetics system for SFTS virus and its application for high throughput drug screening system and functional analysis of the viral proteins of SFTS virus

• Project/Area Number: 15K21645
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Veterinary medical science; Virology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Taniguchi Satoshi 国立感染症研究所, ウイルス第一部, 主任研究官 (60734465)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: SFTSウイルス / ハートランドウイルス / ミニゲノム法 / リンパ球性脈絡髄膜炎ウイルス / 遺伝子操作系 / 蛋白質 / 抗ウイルス薬スクリーニング

Outline of Final Research Achievements

Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV). SFTSV belongs to genus Phlebovirus, family Phenuiviridae. In this study, we tried to establish reverse genetics system for SFTSV to apply this system to a high-throughput drug screening system and functional analysis of viral proteins. However, we couldn’t establish the system. Alternatively, we analyzed the characteristics of SFTSV glycoprotein and developed a new neutralization assay of SFTSV. Furthermore, we analyzed the function of nucleoprotein which is essential for viral genome replication.
Lymphocytic choriomeningitis virus (LCMV) belongs to family Arenaviridae. In this study, we tried to elucidate the role of untranslated regions (UTRs) of LCMV S segment genome. We found that introduction of mutations in the UTR in S segment resulted in attenuation of LCMV. These results suggested LCMVs with mutated UTRs could be a candidate of attenuated LCMV vaccine.

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] First isolation and characterization of pteropine orthoreoviruses in fruit bats in the Philippines. (2017)
  • Author(s): Taniguchi S, Maeda K, Horimoto T, Masangkay JS, Puentespina Jr R., Eres E, et al.
  • Journal Title: Arch Virol Volume: - Issue: 6 Pages: 1529-1539
  • DOI: 10.1007/s00705-017-3251-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] かりフォルニア脳炎オルソブニヤウイルス感染症 (2017)
  • Author(s): 谷口 怜
  • Journal Title: 化学療法の領域 Volume: 33 Pages: 113-121
• [Journal Article] Severe Fever with Thrombocytopenia Syndrome Virus Antigen Detection Using Monoclonal Antibodies to the Nucleocapsid Protein. (2016)
  • Author(s): Fukuma A, Fukushi S, Yoshikawa T, Tani H, Taniguchi S, Kurosu T, Egawa K, Suda Y, Singh H, Nomachi T, Gokuden M, Ando K, Kida K, Kan M, Kato N, Yoshikawa A, Kitamoto H, Sato Y, Suzuki T, Hasegawa H, Morikawa S, Shimojima M, Saijo M
  • Journal Title: PLOS Neglected Tropical Diseases Volume: 10(4) Issue: 4 Pages: e0004595-e0004595
  • DOI: 10.1371/journal.pntd.0004595
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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] Combination effects of ribavirin and interferons on severe fever with thrombocytopenia syndrome virus infection. (2015)
  • Author(s): Shimojima M, Fukushi S, Tani H, Taniguchi S, Fukuma A, Saijo M.
  • Journal Title: Virol J. Volume: 12 Issue: 1 Pages: 181-181
  • DOI: 10.1186/s12985-015-0412-3
  • Peer Reviewed / Open Access
• [Presentation] Comparative analysis of viral replication and transcription function of Severe fever with thrombocytopenia virus and Heartland virus (2017)
  • Author(s): Satoshi Taniguchi, Masayuki Shimojima, Shuetsu Fukushi, Takeshi Kurosu, Hideki Tani, Tomoki Yoshikawa, Shigeru Morikawa, Fumihiro Kato, Takahiro Maeki, Shigeru Tajima, Chang-Kweng Lim, Masayuki Saijo
  • Organizer: 第65回日本ウイルス学会学術集会
• [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: 第65回日本ウイルス学会学術集会
• [Presentation] A non-human primate model for severe fever with thrombocytopenia syndrome SFTS (2017)
  • Author(s): Masayuki Shimojima, Satoshi Taniguchi, Yasushi Ami, Noriyo Nagata, Shuetsu Fukushi, Takeshi Kurosu, Shumpei Watanabe, Hideki Tani, Aiko Fukuma, Naoko Iwata-Yoshikawa, Masayuki Saijo
  • Organizer: 第65回日本ウイルス学会学術集会
• [Presentation] First Isolation and Characterization of Pteropine Orthoreoviruses in Fruit Bats in the Philippines (2017)
  • Author(s): Satoshi Taniguchi, Ken Maeda, Taisuke Horimoto, Joseph S Mansangkay, Roberto Puentespina Jr., Kazutaka Egawa, Shuetsu Fukushi, Yasuhiro Yoshikawa, Masayuki Shimojima, Masayuki Saijo, Shigeru Kyuwa
  • Organizer: 7th International Congress of Virology International Union of Microbiological Societies 2017
  • Int'l Joint Research
• [Presentation] Analysis of the cross reactivity of flaviviruses with Japanese encephalitis patient’s sera showed the importance of neutralization test (2017)
  • Author(s): Takahiro Maeki, Shigeru Tajima, Makiko Ikeda, Fumihiro Kato, Satoshi Taniguchi, Eri Nakayama, Chang-Kweng Lim, Tomohiko Takasaki, Masayuki Saijo
  • Organizer: 第65回日本ウイルス学会学術集会
• [Presentation] The Characterization of large and small plaque variants in Zika virus Chiba isolate ZIKV/Hu/S36/Chiba/2016 (2017)
  • Author(s): Shigeru Tajima, Fumihiro Kato, Eri Nakayama, Yasuhiro Kawai, Kenichi Shibasaki, Masakatsu Taira, Satoshi Taniguchi, Takahiro Maeki, Chang-Kweng Lim, Tomohiko Takasaki, Masayuki Saijo
  • Organizer: 第65回日本ウイルス学会学術集会
• [Presentation] リンパ球性脈絡髄膜炎ウイルスのゲノム末端の非翻訳領域の機能解析 (2015)
  • Author(s): Satoshi Taniguchi, Shuetsu Fukushi, Tomoki Yoshikawa, Hideki Tani, Aiko Fukuma, Masayuki Shimojima, Shigeru Morikawa, Masayuki Saijo
  • Organizer: 第63回日本ウイルス学会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-22
  • Int'l Joint Research
• [Presentation] 1アミノ酸変異によるSFTSウイルスGP蛋白質の細胞融合能の変化 (2015)
  • Author(s): Masayuki Shimojima, Satoshi Taniguchi, Shuetsu Fukushi, Masayuki Saijo
  • Organizer: 第63回日本ウイルス学会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-22
  • Int'l Joint Research