Pathogenicity of a novel bunyavirus STB virus

2018 Fiscal Year Annual Research Report

• Project/Area Number: 16K08041
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: 下島 昌幸 国立感染症研究所, ウイルス第一部, 室長 (10422411)
• Co-Investigator(Kenkyū-buntansha): 谷口 怜 国立感染症研究所, ウイルス第一部, 主任研究官 (60734465) ; 渡辺 俊平 国立感染症研究所, ウイルス第一部, 研究員 (10621401) [Withdrawn]
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ナイロウイルス / STB/ISKウイルス / 病原性 / リアソータント / 日本で分離

Outline of Annual Research Achievements

本研究は日本で分離されたSoft tick bunya (STB)ウイルスについて、そのウイルス学的な性状をIssyk-Kul (ISK)熱の原因ウイルスであるISKウイルスと比較することによってSTBウイルスが日本で熱性疾患を起こしていないか推測し、STBウイルスに対する今後の対
応（新規感染症としての対応もしくはワクチンとしての活用等）に役立てるものである。STBウイルスとISKウイルスとはいずれも分類上はナイロウイルス科に属し、3分節からなるゲノム構造や抗原性が類似することが分かっている。
昨年度までの研究で、両ウイルスの増殖性があるダニ由来細胞で明らかに異なること、IFNAR-/-マウスを死亡させるまでの日数が明らかに異なることが分かっていた。また、両ウイルスからなるキメラウイルス（リアソータント）が作製できていた。
キメラウイルスを用いた解析から、ダニ由来細胞での増殖性の差はウイルスゲノムのL分節に依存することが判明した。マウスでの病原性の差にはS分節が大きくかかわることも判明した。一方、M分節については、いずれのウイルスに由来してもキメラウイルスでは弱毒化することが判明した。
STBウイルスとISKウイルスについて、その性状と関連する責任因子を決定することができた。STBウイルスはISKウイルスより弱毒と言えるが、ワクチンを考えた場合にはM分節をISKウイルスとしたほうがより弱毒化が期待できると考えられた。

Research Products

• [Journal Article] Effects of Soluble Tumor Necrosis Factor (TNF) on Antibody-Dependent Cellular Cytotoxicity of Therapeutic anti-TNF-α Antibody. (2018)
  • Author(s): 2.Hirosaki H, Maeda Y, Shimojima M, Maeda K, Iwata H, Takeyoshi M.
  • Journal Title: Immunol Invest. Volume: 20 Pages: 1-10
  • DOI: 10.1080/08820139.2018.1549067.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Therapeutic effects of favipiravir against severe fever with thrombocytopenia syndrome virus infection in a lethal mouse model: Dose-efficacy studies upon oral administration. (2018)
  • Author(s): 3.Tani H, Komeno T, Fukuma A, Fukushi S, Taniguchi S, Shimojima M, Uda A, Morikawa S, Nakajima N, Furuta Y, Saijo M.
  • Journal Title: PLoS One. Volume: 13 Pages: e0206416.
  • DOI: 10.1371/journal.pone.0206416.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Seroprevalence of severe fever with thrombocytopenia syndrome (SFTS) virus antibodies in humans and animals in Ehime prefecture, Japan, an endemic region of SFTS. (2018)
  • Author(s): 4.Kimura T, Fukuma A, Shimojima M, Yamashita Y, Mizota F, Yamashita M, Otsuka Y, Kan M, Fukushi S, Tani H, Taniguchi S, Ogata M, Kurosu T, Morikawa S, Saijo M, Shinomiya H.
  • Journal Title: J Infect Chemother. Volume: 24 Pages: 802-806
  • DOI: 10.1016/j.jiac.2018.06.007.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Reemergence of Reston ebolavirus in Cynomolgus Monkeys, the Philippines, 2015. (2018)
  • Author(s): 5.Demetria C, Smith I, Tan T, Villarico D, Simon EM, Centeno R, Tachedjian M, Taniguchi S, Shimojima M, Miranda NLJ, Miranda ME, Rondina MMR, Capistrano R, Tandoc A 3rd, Marsh G, Eagles D, Cruz R, Fukushi S.
  • Journal Title: Emerg Infect Dis. Volume: 24 Pages: 1285-1291
  • DOI: 10.3201/eid2407.171234.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] RIG-I-Like Receptor and Toll-Like Receptor Signaling Pathways Cause Aberrant Production of Inflammatory Cytokines/Chemokines in a Severe Fever with Thrombocytopenia Syndrome Virus Infection Mouse Model. (2018)
  • Author(s): 6.Yamada S, Shimojima M, Narita R, Tsukamoto Y, Kato H, Saijo M, Fujita T.
  • Journal Title: J Virol. Volume: 92 Pages: e02246-17.
  • DOI: 10.1128/JVI.02246-17.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Caffeic acid, a coffee-related organic acid, inhibits infection by severe fever with thrombocytopenia syndrome virus in vitro. (2018)
  • Author(s): 7.Ogawa M, Shirasago Y, Ando S, Shimojima M, Saijo M, Fukasawa M.
  • Journal Title: J Infect Chemother. Volume: 24 Pages: 597-601
  • DOI: 10.1016/j.jiac.2018.03.005.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Investigation of antibody to severe fever with thrombocytopenia syndrome virus (SFTSV) in blood samples donated in a SFTS-endemic area in Japan. (2018)
  • Author(s): 8.Matsumoto C, Shinohara N, Furuta RA, Tanishige N, Shimojima M, Matsubayashi K, Nagai T, Tsubaki K, Satake M.
  • Journal Title: Vox Sang. Volume: 113 Pages: 297-299
  • DOI: 10.1111/vox.12629.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The development of a novel diagnostic assay that uses a pseudotyped vesicular stomatitis virus for the detection of neutralising activity to Crimean-Congo haemorrhagic fever virus. (2018)
  • Author(s): 9.Suda Y, Chamberlain J, Dowall S, Saijo M, Horimoto T, Hewson R, Shimojima M.
  • Journal Title: Jpn J Infect Dis. Volume: 71 Pages: 205-208
  • DOI: 10.7883/yoken.JJID.2017.354.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] コンゴ民主共和国の国立生物医学研究所での検査体制とバイオセーフティ (2018)
  • Author(s): 下島昌幸
  • Organizer: 第18回日本バイオセーフティ学会学術集会
• [Presentation] Protection of mice from a lethal challenge with SFTS virus by immunization with a novel recombinant LC16m8 expressing SFTS virus genes. (2018)
  • Author(s): Tomoki Yoshikawa，Satoshi Taniguchi，Hirofumi Kato，Hikaru Fujii，Miho Shibamura，Shumpei Watanabe，Kazutaka Egawa，Takuya Inagaki，Satoko Sugimoto，Supranee Phanthanawiboon，Shizuko Harada，Takeshi Kurosu，Shuetsu Fukushi，Masayuki Shimojima，Souichi Yamada，Shigeru Morikawa，Masayuki Saijo.
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Re-emergence of Reston Ebola virus in Cynomolgus monkeys in the Philippines, 2015. (2018)
  • Author(s): Shuetsu Fukushi，Satoshi Taniguchi，Shumpei Watanabe，Takeshi Kurosu，Tomoki Yoshikawa，Masayuki Shimojima，Shigeru Morikawa，Masayuki Saijo.
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Fusogenic bat-borne orthoreovirus p17 protein regulates viral replication in a host-specific manner. (2018)
  • Author(s): Ryotaro Nouda，Takahiro Kawagishi，Yuta Kanai，Masayuki Shimojima，Masayuki Saijo，Yoshiharu Matsuura，Takeshi Kobayashi.
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Study of the role of untranslated regions of the S segment genome of Lymphocytic Choriomeningitis Virus. (2018)
  • Author(s): Satoshi Taniguchi，Tomoki Yoshikawa，Masayuki Shimojima，Shuetsu Fukushi，Takeshi Kurosu，Hideki Tani，Fumihiro Kato，Takahiro Maeki，Shigeru Tajima，Chang-Kweng Lim，Shigeru Morikawa，Masayuki Saijo.
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] SFTS virus causes lethal severe fever with thrombocytopenia syndrome in Cats. (2018)
  • Author(s): Eun-Sil Park，Masayuki Shimojima，Tomoki Yoshikawa，Noriyo Nagata，Naoko Iwata，Shuetsu Fukushi，Shumpei Watanabe，Yasushi Ami，Takeshi Kurosu，Ken Maeda，Koichi Imaoka，Masayuki Saijo，Shigeru Morikawa.
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Hematopathogenesis of chimeric dengue mouse model. (2018)
  • Author(s): Supranee Phanthanawiboon，Takeshi Kurosu，Masayuki Shimojima，Shuetsu Fukushi，Tomoki Yoshikawa，Shumpei Watanabe，Tadaki Suzuki，Noriyo Nagata， Naoko Iwata-Yoshikawa，Masayuki Saijo.
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Inflammation amplifier plays a critical role in severe dengue hemorrhagic fever. (2018)
  • Author(s): Takeshi Kurosu，Daisuke Okuzaki，Shuetsu Fukushi，Masayuki Shimojima，Supranee Phanthanawiboon，Masayuki Saijo.
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Therapeutic effects of human monoclonal antibodies to SFTS virus. (2018)
  • Author(s): Masayuki Shimojima，Taishi Onodera，Yoshimasa Takahashi，Satoko Sugimoto，Shuetsu Fukushi，Takeshi Kurosu，Tomoki Yoshikawa，Masayuki Saijo.
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Nelson Bay reovirus σC body domain is associated with strain-specific differences in viral replication. (2018)
  • Author(s): Takahiro Kawagishi，Yuta Kanai，Yusuke Sakai，Ryotaro Nouda，Hideki Tani，Masayuki Shimojima，Masayuki Saijo，Yoshiharu Matsuura，Takeshi Kobayashi.
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Caffeic acid, a coffee-related organic acid, inhibits infection with severe fever with thrombocytopenia syndrome virus. (2018)
  • Author(s): Motohiko Ogawa，Yoshitaka Shirasago，Shuji Ando，Masayuki Shimojima，Masayuki Saijo，Masayoshi Fukasawa.
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Establishment of an animal model of Heartland virus infection and evaluation of the efficacy of ribavirin and T-705 in vitro and in vivo. The 66th Annual Meeting of the Japanese Society for Virology. (2018)
  • Author(s): Hikaru Fujii，Hideki Tani，Kazutaka Egawa，Satoshi Taniguchi，Tomoki Yoshikawa，Chang-Kweng Lim，Mutsuyo Takayama-Ito，Takahiro Maeki，Takeshi Kurosu，Shuetsu Fukushi，Masayuki Shimojima，Akihiko Uda，Shigeru Morikawa，Masayuki Saijo.
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Characterization of pseudotyped vesicular stomatitis virus bearing the Heartland virus envelope protein. (2018)
  • Author(s): Miyuki Kimura，Kazutaka Egawa，Masayuki Shimojima，Hikaru Fujii，Hiroshi Yamada，Long Tan，Shigeru Morikawa，Masayuki Saijo，Hideki Tani.
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] 重症熱性血小板減少症候群SFTSの霊長類致死モデル (2018)
  • Author(s): 下島昌幸、谷口怜、網康至、永田典代、福士秀悦、黒須剛、渡辺俊平、谷英樹、福間藍子、岩田奈織子、西條政幸
  • Organizer: SFTS研究会
• [Presentation] SFTSVおよびHRTV感染におけるリバビリンおよびファビピラビルの抗ウイルス効果の比較 (2018)
  • Author(s): 藤井ひかる、谷英樹、谷口怜、吉河智城、林昌宏、伊藤睦代、前木孝洋、黒須剛、福士秀悦、下島昌幸、宇田晶彦、米納孝、古田要介、森川茂、西條政幸
  • Organizer: SFTS研究会
• [Presentation] 重症熱性血小板減少症候群に対するファビピラビルの有効性と安全性の検討 (2018)
  • Author(s): 末盛浩一郎、東太一、山中篤志、姫路大輔、川村昌史、葉久貴司、大毛宏喜、谷口智宏、今滝修、高橋徹、石田正之、日高道弘、金子正彦、池田賢一、上国料千夏、垣花泰之、石丸敏之、竹中克斗、下島昌幸、河野茂、西條政幸、安川正貴
  • Organizer: SFTS研究会
• [Presentation] ミニゲノムを用いたニパウイルス、バングラディシュ株の転写・複製活性の解析 (2018)
  • Author(s): 渡辺俊平、Glenn A. Marsh、黒須剛, 吉河智城, 福士秀悦, 加来義浩,下島昌幸,西條政幸
  • Organizer: 第161回日本獣医学会
• [Presentation] ニパウイルス流行株における転写・複製活性の比較解析 (2018)
  • Author(s): 渡辺俊平、Glenn A. Marsh、黒須剛, 吉河智城, 福士秀悦, 加来義浩,下島昌幸,西條政幸
  • Organizer: 第33回中国四国ウイルス研究会