Nipah virus nucleoprotein inhibits host interferon responses.

• Project/Area Number: 16K08805
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: The University of Tokyo
• Principal Investigator: Sato Hiroki 東京大学, 生産技術研究所, 特任研究員 (50418654)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); 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)
• Keywords: ウイルス / ニパウイルス / N蛋白 / インターフェロン / ニパウイル / 核移行 / ウィルス

Outline of Final Research Achievements

Paramyxoviruses possess negative and single stranded RNA genome, and cause severe pathogenesis against respective natural hosts. There are numerous studies providing evidence for the relationship between P gene products of paramyxoviruses and their antagonistic activities against host interferon (IFN) responses.
In the present study, we revealed that the nucleoprotein (N) of Nipah virus, which belongs to paramyxoviruses, also inhibits the host IFN signaling response. In particular, NiV-N hampered the nuclear transport of STAT1 and STAT2 activated by IFN.
This novel route for preventing host innate immunity by Nipah virus N protein provides new insight into its serious pathogenesis.

Academic Significance and Societal Importance of the Research Achievements

ニパウイルスは1998年にマレーシアで出現したエマージングウイルスで、その後もバングラデシュで毎年流行が報告されており、近年致死率は75%に達している。ニパウイルスはたった8個のウイルス蛋白を産生するが、脳炎をはじめとする激しい病原性を示す。
宿主細胞は、ウイルスの感染に対抗すべくIFN産生を中心とした自然免疫応答を獲得してきたが、ウイルス側も様々なメカニズムでそれらを無効化するよう進化してきた。今回明らかになった、ニパウイルスN蛋白によるIFN応答経路の阻害は、ニパウイルスの病原性の解明の一端につながると考えられ、ニパウイルス感染症の制圧のヒントとなることが期待される。

Research Products

• [Journal Article] Possible role of the Nipah virus V protein in the regulation of the interferon beta induction by interacting with UBX domain-containing protein1 (2018)
  • Author(s): Uchida Shotaro、Horie Ryo、Sato Hiroki、Kai Chieko、Yoneda Misako
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 7682-7682
  • DOI: 10.1038/s41598-018-25815-9
  • Peer Reviewed / Open Access
• [Journal Article] Nipah and Hendra Virus Nucleoproteins Inhibit Nuclear Accumulation of STAT1 and STAT2 by Interfering with Their Complex Formation. (2017)
  • Author(s): Sugai A, Sato H, Takayama I, Yoneda M and Kai C.
  • Journal Title: Journal of Virology Volume: 91 (21) Issue: 21
  • DOI: 10.1128/jvi.01136-17
  • Peer Reviewed / Open Access
• [Presentation] For a veterinary clinical study of a recombinant measles virus in dog cancer patients. (2018)
  • Author(s): Sato H, Fujiyuki T, Shoji K, Amagai Y, Iizuka K, Horikirizono Y, Asano K, Yoneda M, Kai C.
  • Organizer: 11th, International Oncolytic Virus Conference
  • Int'l Joint Research
• [Presentation] Measles virus infection triggers cGAS-dependent antiviral responses. (2018)
  • Author(s): Sato H, Ikeda F, Hoshi M, Yoneda M, Kai C.
  • Organizer: XIX International Meeting on Negative Strand Viruses
  • Int'l Joint Research
• [Presentation] 麻疹ウイルスNタンパク質のリン酸化就職に対する阻害薬の探索 (2018)
  • Author(s): 菅井亮宏、佐藤宏樹、米田美佐子、甲斐知惠子
  • Organizer: 第６６回日本ウイルス学会学術集会
• [Presentation] Nucleocapsid protein of Nipah virus downregulates interferon stimulated genes by inhibiting the nuclea accumulation of STATs. (2017)
  • Author(s): Sugai A., Sato H., Takayama I., Yoneda M. and Kai C.
  • Organizer: XVIIth International Congress of Virology
  • Int'l Joint Research