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2008 Fiscal Year Annual Research Report

ウイルス感染のRNA応答

Research Project

Project/Area Number 19041002
Research InstitutionHokkaido University

Principal Investigator

瀬谷 司  Hokkaido University, 大学院・先端生命科学研究院, 教授 (10301805)

KeywordsRNAアジュバント / Toll-like-receptor / RNAウイルス / インターフェロン / 細胞性免疫 / HCV / poliovirus
Research Abstract

H20年度は以下の2点についてそれぞれ成果を得た。以下に列記する。
1. DI RNAによる樹状細胞を介したNK細胞活性化解析 : Defective interference(DI) RNAは感染のIFN-beta応答においてRIG-I/MDA5をセンサーとする。DI RNAがpolyI : Cと異なりTLR3活性化に向かわない訳はendosomeに行かないためである。PolyI : Cはcytokine stormなど有害事象を誘起するが、DI RNAを含むウイルスワクチンは毒性が低い。PolyI : Cをエンドソーム標的型リポソームにくるんでマウス骨髄樹状細胞(mDC)に投与するとmDCのTLR3を選択活性化出来る事が判明した。IPS-1経路とTICAM-1経路の活性化が誘起する樹状細胞応答(NK活性化など)を比較検討する企画を推進中である。種々の人工合成stem-loop RNAもこの系でテストする。毒性が低くmDCを成熟化させるRNA誘導体をこの系で抽出する事を試みている。
2. ウイルス感染モデルを用いたRNA応答の解析 : 麻疹ウイルスの他にdsRNAを産生するpoliovtrus, HCVを用いて宿主RNA応答を解析した。麻疹DI RNAはRIG-I/MDA5をレセプターとしてIFN誘導を行うことが判明したが、ポリオ、HCVでは他のRNA認識パターン認識レセプター(TLR3, TLR7, TILR8, PKR, dicer-RNAi)を活性化しうるという結果を得た。HCVはhepatocytesに包まれたウイルスRNAがヒトmDCに侵食されてendosomeに到達しそこでTLR3と邂逅する、という経路で外因性のRNA認識経路(TICAM-1経路)を活性化すること、その結果樹状細胞は成熟化してNK, Th1の活性化を誘導する事を証明した(Ebihara et.al., Hepatology 2008)。Poliovtrusは腹腔投与でTICAM-1経路を活性化し、外因性のウイルス応答を誘起することが示された(Matsuo et.al., submitted)。TLR22が樹状細胞に表在するTGマウスを作成して、外因性経路の関与を検討中である。

  • Research Products

    (20 results)

All 2009 2008

All Journal Article (20 results) (of which Peer Reviewed: 20 results)

  • [Journal Article] Pan-vertebrate Toll-like receptors during evolution(review)2009

    • Author(s)
      Oshiumi, H., Seva, T. et.al.
    • Journal Title

      Curr. Genomics 9

      Pages: 488-493

    • Peer Reviewed
  • [Journal Article] Riplet/RNF135, a RING-finger protein, ubiquitinates RIG-I to promote interferon-β induction during the early phase of viral infection2009

    • Author(s)
      Oshiumi, H., Seva, T. et.al.
    • Journal Title

      J. Biol. Chem 284

      Pages: 807-817

    • Peer Reviewed
  • [Journal Article] Obstructing shedding of the immune stimulatory MHC class I chain-related gene B prevents tumor formation2009

    • Author(s)
      Wu, J. D., Seva, T. et.al.
    • Journal Title

      Clin. Cancer Res 15

      Pages: 632-640

    • Peer Reviewed
  • [Journal Article] Functional evolution of the TICAM-1 (TRIF) pathway for extrinsic RNA sensing(review)2009

    • Author(s)
      Seya, T. et.al.
    • Journal Title

      Immunol. Rev 227

      Pages: 44-53

    • Peer Reviewed
  • [Journal Article] Innate immune therapy with a BCG cell wall skeleton after radical surgery for non-small cell lung cancer : a case-control study2009

    • Author(s)
      Kodama, K., Seva, T. et.al.
    • Journal Title

      Surgery Today 39

      Pages: 194-200

    • Peer Reviewed
  • [Journal Article] The extrinsic RNA-sensing pathway for adjuvant immunotherapy of cancer(review)2009

    • Author(s)
      Seya, T. et.al.
    • Journal Title

      Cancer Immunol. Immunother (in press)

    • Peer Reviewed
  • [Journal Article] NK cell licensing by dendritic cell in RNA virus infection(review)2009

    • Author(s)
      Ebihara, T., Seva, T. et.al.
    • Journal Title

      Curr. Immunol. Rev. (in press)

    • Peer Reviewed
  • [Journal Article] Regulator of Complement Activation (RCA) gene cluster in Xenopus tropicalis2009

    • Author(s)
      Oshiumi, H., Seva, T. et.al.
    • Journal Title

      Immunogenetics (in press)

    • Peer Reviewed
  • [Journal Article] Asp-Glu-Ala-Asp/His (DEAD/H) BOX 3 (DDX3) helicase assembles in the IFN-β promoter stimulator-1 (IPS-1) pathway to enhance IFN-β induction2009

    • Author(s)
      Oshiumi, H., Seva, T. et.al.
    • Journal Title

      PloS Pathol (submitted)

    • Peer Reviewed
  • [Journal Article] Specific recognition of diamilopimeric acid-containing peptidoglycan of Gram-negative bacteria by teleost Toll-like receptor 212009

    • Author(s)
      Matsuo, A., Seva, T. et.al.
    • Journal Title

      PloS ONE (submitted)

    • Peer Reviewed
  • [Journal Article] Antitumor natural killer cell induction by orally administered Spirulina extract in mice2009

    • Author(s)
      Akao, Y., Seva, T. et.al.
    • Journal Title

      Cancer Sci (submitted)

    • Peer Reviewed
  • [Journal Article] Tumor-secreted lactic acid promotes IL-23-IL-17 proinflammatory pathway2008

    • Author(s)
      Shime, H., Seva, T. et.al.
    • Journal Title

      J. Immunol 180

      Pages: 7175-7183

    • Peer Reviewed
  • [Journal Article] Teleost TLR22 recognizes RNA duplex to induce IFN and protect cells from birnaviruses2008

    • Author(s)
      Matsuo, A., Seva, T. et.al.
    • Journal Title

      J. Immunol 181

      Pages: 3474-3485

    • Peer Reviewed
  • [Journal Article] Increased expression of Toll-like receptor3 in intrahepatic biliary epithelial cells at sites of ductular reaction in diseased livers2008

    • Author(s)
      Nakamura, M., Seva, T. et.al.
    • Journal Title

      Hepatology International 2

      Pages: 222-230

    • Peer Reviewed
  • [Journal Article] Homo-oligomerization is essential for Toll/IL-1 receptor domain containing adaptor molecule-l-mediated NF-kappaB and interferon regulatory factor-3 activation2008

    • Author(s)
      Funami K., Seva, T. et.al.
    • Journal Title

      J. Biol. Chem 283

      Pages: 18283-18291

    • Peer Reviewed
  • [Journal Article] Modulation of Double-stranded RNA Recognition by the N-terminal Histidine-rich Region of the Human Toll-like Receptor 32008

    • Author(s)
      Fukuda, K., Seya, T. et.al.
    • Journal Title

      J. Biol. Chem 283

      Pages: 22787-22794

    • Peer Reviewed
  • [Journal Article] Hepatitis C virus (HCV)-infected hepatocytes extrinsically modulate dendritic cell maturation to activate T cells and NK cells2008

    • Author(s)
      Ebihara, T., Seya, T. et.al.
    • Journal Title

      Hepatology 48

      Pages: 48-58

    • Peer Reviewed
  • [Journal Article] Soluble G protein of respiratory syncytial virus inhibts Toll-like receptor 3/4-mediated IFN-beta induction2008

    • Author(s)
      Shingai, M., Seya, T. et.al.
    • Journal Title

      Int. Immunol 20

      Pages: 1169-1180

    • Peer Reviewed
  • [Journal Article] Selective synergy in anti-inflammatory cytokine production upon cooperated signaling via TLR4 and TLR2 in murine conventional dendritic cells2008

    • Author(s)
      Hirata, N., Seva, T. et.al.
    • Journal Title

      Mol. Immunol 45

      Pages: 2734-2742

    • Peer Reviewed
  • [Journal Article] The clathrin-mediated endocytic pathway participates in dsRNA-induced IFN-β production2008

    • Author(s)
      Itoh, K., Seva, T. et.al.
    • Journal Title

      J. Immunol 181

      Pages: 5522-5529

    • Peer Reviewed

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Published: 2010-06-11   Modified: 2016-04-21  

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