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Elucidation of the mechanism underlying core histone-mediated antiviral innate immune response

Research Project

Project/Area Number 20590477
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionYokohama City University

Principal Investigator

TAKESHITA Fumihiko  Yokohama City University, 医学研究科, 客員教授 (60333572)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords感染防御 / ウイルス学 / 基礎医学 / ヒストン / 自然免疫 / 免疫調節薬
Research Abstract

Previous our research has clarified that H2B could sense viral double stranded DNA (dsDNA), and induce antiviral innate immune response. The goal of current research is to elucidate molecular mechanism of H2B-mediated recognition of cytoplasmic DNA.
The results showed that extranuclear H2B interacts with IPS-1 upon sensing cytoplasmic DNA. We also identified the novel adaptor molecule, named as CIAO, to connect H2B with IPS-1, and showed that H2B-CIAO-IPS-1 complex has an important role to induce type I IFNs upon antiviral innate immune response. Furthermore, chimera protein N'-CARD, that is constructed by fusion of H2B fragment to IPS-1 fragment, could induce strong type I IFNs production, suggesting that H2B-CIAO-IPS-1 complex could be useful target to develop the novel immunomodulating drugs.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (25 results)

All 2011 2010 2009 2008

All Journal Article (16 results) (of which Peer Reviewed: 7 results) Presentation (6 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] NLRP4 negatively regulates autophagic processes through an association with beclin1.2011

    • Author(s)
      Nao Jounai
    • Journal Title

      Journal of immunology

      Volume: 186 Pages: 1646-1655

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulation of intracellular signaling using protein-transduction technology.2010

    • Author(s)
      Kobiyama, K., N. Jounai, K.J. Ishii, T. Horii, K. Suzuki, A. Ryo, F. Takeshita
    • Journal Title

      Crit Rev Immunol 30

      Pages: 395-421

    • Related Report
      2010 Final Research Report
  • [Journal Article] Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9.2010

    • Author(s)
      Coban, C., Y. Igari, M. Yagi, T. Reimer, S. Koyama, T. Aoshi, K. Ohata, T. Tsukui, F. Takeshita, K. Sakurai, T. Ikegami, A. Nakagawa, T. Horii, G. Nunez, K.J. Ishii, S. Akira
    • Journal Title

      Cell Host Microbe 7

      Pages: 50-61

    • Related Report
      2010 Final Research Report
  • [Journal Article] Extrachromosomal histone H2B mediates innate antiviral immune responses induced by intracellular double-stranded DNA.2010

    • Author(s)
      Kobiyama, K., F. Takeshita, N. Jounai, A. Sakaue-Sawano, A. Miyawaki, K.J. Ishii, T. Kawai, S. Sasaki, H. Hirano, N. Ishii, K. Okuda, K. Suzuki
    • Journal Title

      J Virol 84

      Pages: 822-832

    • Related Report
      2010 Final Research Report
  • [Journal Article] Mutant mouse p53 transgene elevates the chemical induction of tumors that respond to gene silencing with siRNA.2010

    • Author(s)
      Tanooka, H., K. Tatsumi, H. Tsuji, Y. Noda, T. Katsube, H. Ishii, A. Ootsuyama, F. Takeshita, T. Ochiya
    • Journal Title

      Cancer Gene Ther 17

      Pages: 1-10

    • Related Report
      2010 Final Research Report
  • [Journal Article] C/EBPδ and STAT-1 Are Required for TLR8 Transcriptional Activity2010

    • Author(s)
      Claudia Zannetti
    • Journal Title

      Journal of Biological Chemistry

      Volume: 285 Pages: 34773-34780

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulation of intracellular signaling using protein-transduction technology2010

    • Author(s)
      Kouji Kobiyama
    • Journal Title

      Critical Reviews Immunology

      Volume: 30 Pages: 395-421

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Extrachromosomal histone H2B mediates innate antiviral immune responses induced by intracellular double-stranded DNA2010

    • Author(s)
      小檜山康司
    • Journal Title

      Journal of Virology 84号

      Pages: 822-832

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunogeneicity of Whole-Parasite Vaccine against Plasmodium falciparum involves Mararial Hemozoin and Host TLR92010

    • Author(s)
      Cevayir Coban
    • Journal Title

      Cell Host & Microbe 7号

      Pages: 50-61

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Tryptophan aspartate-containing coat protein (CORO1A) suppresses Toll-like receptor signalling in Mycobacterium leprae infection.2009

    • Author(s)
      Tanigawa, K., K. Suzuki, H. Kimura, F. Takeshita, H. Wu, T. Akama, A. Kawashima, N. Ishii
    • Journal Title

      Clin Exp Immunol 156

      Pages: 495-501

    • Related Report
      2010 Final Research Report
  • [Journal Article] A signaling polypeptide derived from an innate immune adaptor molecule can be harnessed as a new class of vaccine adjuvant.2009

    • Author(s)
      Kobiyama, K., F. Takeshita, K. J. Ishii, S. Koyama, T. Aoshi, S. Akira, A. Sakaue-Sawano, A. Miyawaki, Y. Yamanaka, H. Hirano, K. Suzuki, K. Okuda
    • Journal Title

      J Immunol 182

      Pages: 1593-1601

    • Related Report
      2010 Final Research Report
  • [Journal Article] A signaling polypeptide derived from an innate immune adaptor molecule can be harnessed as a new class of vaccine adjuvant.2009

    • Author(s)
      Kobiyama K, Takeshita F*, Ishii KJ, Koyama S, Aoshi T, Akira S, Sakaue-Sawano A, Miyawaki A, Yamanaka Y, Hirano H, Suzuki K, Okuda K.
    • Journal Title

      Journal of Immunology 182

      Pages: 1593-1601

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular DNA sensors in immunity.2008

    • Author(s)
      F. Takeshita, K. J. Ishii
    • Journal Title

      Curr Opin Immunol 20

      Pages: 383-388

    • Related Report
      2010 Final Research Report
  • [Journal Article] Molecular and cellular mechanisms of DNA vaccines.2008

    • Author(s)
      Coban, C., S. Koyama, F. Takeshita, S. Akira, K.J. Ishii
    • Journal Title

      Hum Vaccin 4

      Pages: 453-456

    • Related Report
      2010 Final Research Report
  • [Journal Article] Molecular and cellular mechanisms of DNA vaccines.2008

    • Author(s)
      Coban C, Koyama S, Takeshita F, Akira s, Ishii KJ.
    • Journal Title

      Human Vaccine 4

      Pages: 453-456

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular DNA sensors in immunity.2008

    • Author(s)
      Takeshita F*, Ishii KJ.
    • Journal Title

      Current Opinion in Immunology 20

      Pages: 383-388

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] NLRP4 negatively regulates autophagic process through an association with Beclin1.2010

    • Author(s)
      Nao Jounai
    • Organizer
      The 16^<th> Takeda Science Foundation Symposium on Bioscience "Casting light on life"
    • Place of Presentation
      Sheraton Miyako Hotel東京
    • Year and Date
      2010-12-01
    • Related Report
      2010 Annual Research Report
  • [Presentation] A signaling polypeptide derived from an innate immune adaptor molecule can be harnessed as a new class of vaccine adjuvant.2009

    • Author(s)
      武下文彦, 小檜山康司
    • Organizer
      International Workshop co-sponsored by Yokohama City University & FDA.
    • Place of Presentation
      Yokohama
    • Year and Date
      2009-04-04
    • Related Report
      2010 Final Research Report
  • [Presentation] A signaling polypeptide derived from an innate immune adaptor molecule can be harnessed as a new class of vaccine adjuvant.2009

    • Author(s)
      Kobiyatna K, Ishii KJ, Takeshita F.
    • Organizer
      Keystone Symposia on Molecular and Cellular Biology.
    • Place of Presentation
      カナダ、パンフ
    • Year and Date
      2009-03-29
    • Related Report
      2008 Annual Research Report
  • [Presentation] A signaling polypeptide derived from an innate immune adaptor molecule can be harnessed as a new class of vaccine adjuvant.2009

    • Author(s)
      小檜山康司, 石井健, 武下文彦
    • Organizer
      Keystone Symposia on Molecular and Cellular Biology.
    • Place of Presentation
      Banff, Alberta, Canada
    • Related Report
      2010 Final Research Report
  • [Presentation] 自然免疫活性化機序の解明と応用2009

    • Author(s)
      武下文彦
    • Organizer
      第8回プロテオーム医療創薬研究会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] IPS-1変異体による新規自然免疫活性化メカニズムの解析および免疫調節薬への応用2008

    • Author(s)
      小檜山康司、武下文彦、石井健、鈴木幸一、奥田研爾
    • Organizer
      第19回日本生体防御学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] 染色体外ヒストンH2Bを介する二本鎖DNA認識機構の利用2009

    • Inventor(s)
      武下文彦、小檜山康司、吉田篤司
    • Industrial Property Rights Holder
      公立大学法人 横浜市立大学
    • Patent Publication Number
      2011-109982
    • Filing Date
      2009-11-27
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] カスパーゼリクルートメントドメインを応用した新規リコンビナントタンパク及びその用途2009

    • Inventor(s)
      武下文彦、小檜山康司、奥田研爾
    • Industrial Property Rights Holder
      公立大学法人 横浜市立大学
    • Filing Date
      2009-08-12
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] カスパーゼリクルートメントドメインを応用した新規リコンビナントタンパク及びその用途2008

    • Inventor(s)
      武下文彦小檜山康司奥田研爾
    • Industrial Property Rights Holder
      横浜市立大学
    • Filing Date
      2008-08-29
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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