Novel mechanisms of cellular antiviral defense through the PARP-13 shorter isoform, ZAPS

• Project/Area Number: 25713032
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Tokyo Medical and Dental University (2014-2016); Hokkaido University (2013)
• Principal Investigator: HAYAKAWA Sumio 東京医科歯科大学, 難治疾患研究所, 助教 (00368292)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥25,090,000 (Direct Cost: ¥19,300,000、Indirect Cost: ¥5,790,000); Fiscal Year 2015: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000); Fiscal Year 2014: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2013: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: インターフェロン / インフルエンザウイルス / 抗ウイルス / 自然免疫

Outline of Final Research Achievements

Type I IFN are produced in response to viral infection and are key cytokines for the activation of innate immunity. The pathogen invasion is sensed by pattern-recognition receptors(PRRs) of innate immune system through the recognition of pathogen associated molecular patterns(PAMPs). The PRRs trigger the activation of intracellular signaling pathway, which leads to the induction of antimicrobial genes. RIG-I is the key PRR for detection of positive- and negative strand RNA viruses in the cytoplasm of cells and has an important triggering response to viruses, such as influenza A virus. However, the NS1 from influenza virus counters host antiviral defenses. In this study, the interaction of RIG-I and ZAPS is one of the keypoints, wherein NS1 inhibits RIG-I-mediated antiviral activity.

Research Products

• [Journal Article] Constitutive aryl hydrocarbon receptor signaling constrains type I interferon-mediated antiviral innate defense. (2016)
  • Author(s): Yamada T, Horimoto H, Kameyama T, Hayakawa S, Yamato H, Dazai M, Takada A, Kida H, Bott D, Zhou AC, Hutin D, Watts TH, Asaka M, Matthews, Takaoka A
  • Journal Title: Nat Immunol. Volume: 印刷中 Issue: 6 Pages: 687-694
  • DOI: 10.1038/ni.3422
  • NAID: 120005849912
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Constitutive aryl hydrocarbon receptor signaling constrains antiviral IFN response thorough TIPARP induction (2016)
  • Author(s): Yamada T., Horimoto H., Kameyama T., Hayakawa S. and Takaoka A.
  • Organizer: the 24th International Symposium on Molecular Cell Biology of Macrophages (MMCB2016)
  • Place of Presentation: Sola City Conference Center, Tokyo
  • Year and Date: 2016-06-04
  • Int'l Joint Research
• [Presentation] 炎症シグナルが調節する脂質代謝調節機構 (2015)
  • Author(s): 早川清雄，今野太貴，星野由紀子，大石由美子
  • Organizer: 第38回 日本分子生物学会年会/第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-02
• [Presentation] ZAPS と IAV 由来 NS1 の競合による自然免疫回避機構の検討 (2014)
  • Author(s): 早川清雄，山田大翔，亀山武志，喜田宏，宮崎忠昭，髙岡晃教
  • Organizer: 第７９回日本インターフェロン・サイトカイン学会 学術集会
  • Place of Presentation: 北海道大学医学部学友会館
  • Year and Date: 2014-06-19 – 2014-06-20
• [Presentation] Influenza virus NS1 protein counteracts ZAPS function to evade RIG-I-mediated antiviral defence. (2013)
  • Author(s): S.Hayakawa, T.Kameyama, T.Yamada, A. Takaoka
  • Organizer: 15th INTERNATIONAL CONGRESS OF IMMUNOLOGY
  • Place of Presentation: MiCo - Milano Congressi, Milan, Italy