Screening of novel tick-borne phlebovirus and virulence factor of SFTS virus

• Project/Area Number: 16K18791
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Veterinary medical science
• Research Institution: Hokkaido University
• Principal Investigator: MATSUNO Keita 北海道大学, 獣医学研究院, 特任講師 (40753306)
• Research Collaborator: Kajihara Masahiro ; Ebihara Hideki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ダニ媒介性ウイルス / 病原性獲得 / フレボウイルス / 多様性 / 病原性 / ウイルス / ダニ媒介性 / 進化 / ウィルス / 獣医学 / 衛生 / 感染症

Outline of Final Research Achievements

Sever fever with thrombocytopenia syndrome (SFTS) virus causes fatal febrile illness in humans and has obtained lots of attention in Eastern Asia, including Japan. In the present study, the present study aims to reveal the evolutional process in which SFTS virus increases its virulence to humans by comparing tick-borne phleboviruses closely related to SFTS virus. Novel tick-borne phleboviruses were identified in Japan and also in abroad, and wild animals were suggested to be infected with these viruses. Tick-borne phleboviruses seem to coevolve with ticks, and acquisition of NSs gene could be associated with SFTS virus virulence.

Academic Significance and Societal Importance of the Research Achievements

本研究により、日本国内外のダニ媒介性フレボウイルスの浸潤状況が明らかとなった。これらのウイルスはヒトや動物に対する病原性は不明だが、さまざまウイルスが発見されたことで不明熱の診断の一助となるかもしれない。野生動物がこれらのフレボウイルスに感染していることも分かったため、今後、どのような動物がフレボウイルスに感染するかを調べ、病気との関連を研究することができる。また、西日本で問題となっているSFTSウイルスが病気を起こすためには、NSsと呼ばれるタンパク質をコードする遺伝子が必要であることが示唆された。ウイルスの進化と病原性獲得を議論する上で重要な知見となる。

Research Products

• [Int'l Joint Research] メイヨークリニック(米国)
• [Int'l Joint Research] ガブリエル・レネ・モレノ自治大学(ボリビア)
• [Int'l Joint Research] シエラレオネ大学(シエラレオネ)
• [Int'l Joint Research] ザンビア大学(ザンビア)
• [Int'l Joint Research] ミャンマー獣医科大学(ミャンマー)
• [Int'l Joint Research] メイヨークリニック(米国)
• [Int'l Joint Research] 南太平洋大学(フィジー)
• [Int'l Joint Research] ザンビア大学(ザンビア)
• [Int'l Joint Research] ミャンマー獣医科大学(ミャンマー)
• [Int'l Joint Research] Rocky Mountain Laboratories, NIAID, NIH/Mayo clinic(米国)
• [Int'l Joint Research] University of Zambia(ザンビア)
• [Int'l Joint Research] University of South Pacific(フィジー)
• [Int'l Joint Research] ミャンマー獣医科学大学(ミャンマー)
• [Int'l Joint Research] モンゴル国立農業大学獣医学研究所(モンゴル)
• [Journal Article] Infection of newly identified phleboviruses in ticks and wild animals in Hokkaido, Japan indicating tick-borne life cycles (2019)
  • Author(s): Torii Shiho、Matsuno Keita、Qiu Yongjin、Mori-Kajihara Akina、Kajihara Masahiro、Nakao Ryo、Nao Naganori、Okazaki Katsunori、Sashika Mariko、Hiono Takahiro、Okamatsu Masatoshi、Sakoda Yoshihiro、Ebihara Hideki、Takada Ayato、Sawa Hirofumi
  • Journal Title: Ticks and Tick-borne Diseases Volume: 10 Issue: 2 Pages: 328-335
  • DOI: 10.1016/j.ttbdis.2018.11.012
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fatal Tickborne Phlebovirus Infection in Captive Cheetahs, Japan (2018)
  • Author(s): Matsuno Keita、Nonoue Noriyuki、Noda Ayako、Kasajima Nodoka、Noguchi Keita、Takano Ai、Shimoda Hiroshi、Orba Yasuko、Muramatsu Mieko、Sakoda Yoshihiro、Takada Ayato、Minami Shinji、Une Yumi、Morikawa Shigeru、Maeda Ken
  • Journal Title: Emerging Infectious Diseases Volume: 24 Issue: 9 Pages: 1726-1729
  • DOI: 10.3201/eid2409.171667
  • NAID: 120006529645
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Unique Phylogenetic Position of a Novel Tick-Borne Phlebovirus Ensures an Ixodid Origin of the Genus Phlebovirus (2018)
  • Author(s): Matsuno Keita、Kajihara Masahiro、Nakao Ryo、Nao Naganori、Mori-Kajihara Akina、Muramatsu Mieko、Qiu Yongjin、Torii Shiho、Igarashi Manabu、Kasajima Nodoka、Mizuma Keita、Yoshii Kentaro、Sawa Hirofumi、Sugimoto Chihiro、Takada Ayato、Ebihara Hideki
  • Journal Title: mSphere Volume: 3 Issue: 3
  • DOI: 10.1128/msphere.00239-18
  • NAID: 120006501204
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Animal Models of Emerging Tick-Borne Phleboviruses: Determining Target Cells in a Lethal Model of SFTSV Infection. (2017)
  • Author(s): Matsuno K, Orba Y, Maede-White K, Scott D, Feldmann F, Liang M, Ebihara H.
  • Journal Title: Front Microbiol. Volume: 8 Pages: 104-104
  • DOI: 10.3389/fmicb.2017.00104
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Putative RNA viral sequences detected in an Ixodes scapularis-derived cell line. (2016)
  • Author(s): Nakao R, Matsuno K, Qiu Y, Maruyama J, Eguchi N, Nao N, Kajihara M, Yoshii K, Sawa H, Takada A, Sugimoto C.
  • Journal Title: Ticks Tick Borne Dis. Volume: 8 Issue: 1 Pages: 103-111
  • DOI: 10.1016/j.ttbdis.2016.10.005
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Complete mitochondrial genome analysis of ticks (2018)
  • Author(s): Ryo Nakao, Gohta Kinoshita, Ayumi Saito, Yongjin Qiu, Keita Matsuno, Chihiro Sugimoto, Ken Katakura
  • Organizer: 14th International Congress of Parasitology (ICOPA 2018)(国際学会)
  • Int'l Joint Research
• [Presentation] In-depth analysis of viral and host RNAs interacting with severe fever with thrombocytopenia syndrome virus (SFTSV) nucleoprotein N (2018)
  • Author(s): Keita Mizuma, Keita Matsuno, Masatoshi Okamatsu, Ayato Takada, Yoshihiro Sakoda
  • Organizer: 日本ウイルス学会北海道支部 平成30年度 夏季シンポジウム
• [Presentation] ブニヤウイルスの遺伝的多様性から紐解く病原性 (2017)
  • Author(s): 松野 啓太
  • Organizer: ウイルス研究の潮流シリーズセミナー
  • Invited
• [Presentation] Genetic diversity among phleboviruses identified in ticks; implication of distinct evolutional pathways of phleboviruses (2017)
  • Author(s): Keita Matsuno, Masahiro Kajihara, Nodoka Kasajima, Ryo Nakao, Shiho Torii, Hiroshi Shimoda, Ken Maeda, Ayato Takada, Hideki Ebihara, Hirofumi Sawa
  • Organizer: 第16回あわじしま感染症・免疫フォーラム
  • Int'l Joint Research / Invited
• [Presentation] 動物園におけるダニ媒介性ウイルス感染症によるチーターの死亡 (2017)
  • Author(s): 松野 啓太, 笠島 和, 野々上範之, 野田亜矢子, 南 心司, 宇根有美, 前田 健
  • Organizer: 第63回日本寄生虫学会・日本衛生動物学会北日本支部合同大会
• [Presentation] Discovery and characterization of novel tick-borne phleboviruses in ticks collected in Hokkaido (2017)
  • Author(s): Shiho Torii, Keita Matsuno, Masahiro Kajihara, Ryo Nakao, Naganori Nao, Yongjin Qiu, Manabu Igarashi, Akina Mori-Kajihara, Mieko Muramatsu, Kentaro Yoshii, Chihiro Sugimoto, Ayato Takada, Hirofumi Sawa, Hideki Ebihara
  • Organizer: 第16回あわじしま感染症・免疫フォーラム
  • Int'l Joint Research
• [Presentation] 2つの現場から：ダニ媒介性ウイルスの網羅的探索と鳥インフルエンザの診断 (2017)
  • Author(s): 松野啓太
  • Organizer: 第6回生命医薬情報学連合大会
• [Presentation] Discoveries of novel viruses in ticks and fruit bats by using FLDS method and MinION sequencer (2017)
  • Author(s): Keita Matsuno, Masahiro Kajihara, Syun-ichi Urayama, Ryo Nakao, Miho Hirai, Yongjin Qiu, Takuro Nunoura, Aaron S Mweene, Bernard M Hang'ombe, Martin Simuunza, Masatoshi Okamatsu, Yoshihiro Sakoda, Hirofumi Sawa, Ayato Takada
  • Organizer: 第65回日本ウイルス学会学術集会
  • Int'l Joint Research
• [Presentation] Suppression of PKR signaling pathway by nonstructural protein of severe fever with thrombocytopenia syndrome virus. (2017)
  • Author(s): Kasajima N, Matsuno K, Torii S, Hiono T, Okamatsu M, Ebihara H, Sakoda Y
  • Organizer: 第65回日本ウイルス学会学術集会
  • Int'l Joint Research
• [Presentation] The animal models for the emerging tick-borne phleboviruses: identification of target cells in a lethal model of SFTSV infection (2016)
  • Author(s): Keita Matsuno, Yasuko Orba, Kimberly Maede-White, Dana Scott, Friederike Feldmann, Hirofumi Sawa, Hideki Ebihara
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-10-23
  • Int'l Joint Research
• [Presentation] マダニ中に見られるフレボウイルスの遺伝的多様性 (2016)
  • Author(s): 松野 啓太, 下田 宙, 鳥居 志保, 邱 永晋, Brandi Williamson, 中尾 亮, 梶原 将大, 岡松 正敏, 迫田 義博, 奥村 敦, 高田 礼人, 澤 洋文, Tom Schwan, 前田 健, 海老原 秀喜
  • Organizer: 第24回ダニと疾患のインターフェースに関するセミナー
  • Place of Presentation: 休暇村指宿（鹿児島県指宿市）
  • Year and Date: 2016-05-27