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Mechanism by which Sendai virus inhibits interferon signaling

Research Project

Project/Area Number 13670294
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research Institution福井医科大学

Principal Investigator

GOTOH Bin  University of Fukui, Faculty of Medical Sciences, Associate Professor, 医学部, 助教授 (00211920)

Co-Investigator(Kenkyū-buntansha) TAKEUCHI Kenji  University of Fukui, Faculty of Medical Sciences, Associate Professor, 医学部, 助手 (40236419)
KOMATSU Takayuki  University of Fukui, Faculty of Medical Sciences, Associate Professor, 医学部, 助手 (20215388)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsSendai virus / C protein / accessory proteins / STAT1 / STAT2 / Interferon / signaling / phosphorylation / GAF / GAS / パラミクソウイルス / STATs / 免疫回避
Research Abstract

Infection with Sendai virus (SeV) renders cells unresponsive to interferon (IFN). The antagonism to IFN is due to the functions of C protein, which is viral accessory protein encoded by the SeV P gene. Our studies have revealed a molecular basis for the mechanism by which SeV inhibits IFN signaling : 1. SeV C protein binds to the signal transducer and activator of transcription (STAT) 1, a key factor on the IFN signaling pathways, resulting in formation of C-STAT1 high molecular mass complexes under the law salt conditions. 2. The C-terminal half domain of the C protein interacts with the N-terminal domain of STAT1. 3.C protein affects IFN-stimulated phosphorylation of STATs including STAT1, STAT2, and STAT3. 4. C protein impairs the STAT1 dephosphorylation event. 5. Binding of IFN-α to the type I IFN receptor on the cell surface causes tyrosine phosphorylation of STAT1 and STAT2. The IFN-α stimulated tyrosine phosphorylation of STAT2 is completely inhibited by C protein. This complete inhibition is essential for the blockade of IFN-α signaling. 6. Mechanism by which C protein inhibits the IFN-γ response is different from the anti-IFN-α mechanism. C protein allows STAT1 to be phosphorylated at both Tyr^<701> and Ser^<727>. The C-terminal half fragment of C protein, which has the anti-IFN-γ ability comparable to that of the full-size C, prevents the gamma-activated factor (GAF) from binding to a gamma-activated sequence (GAS) site in vitro. This suggests the possibility that the C protein inhibits the GAF-GAS binding through the interaction with STAT1. 7. We found that a C variant with no STAT1-binding property could inhibit the IFN-γ response but not the IFN-α response. This novel mechanism independent of the STAT1-binding remains to be solved.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Kenji Takeuchi: "Sendai virus C protein physically associates with Stat 1."Genes Cells. 6. 545-557 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Bin Gotoh: "Paramyxovirus accessory proteins as interferon antagonists."Microbiol.Immunol.. 45. 787-800 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takaynki Komatsu: "Sendai virus C protein impairs both phosphorylation and dephosphorylation processes of Stat 1."FEBS Letters. 511. 139-144 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Bin Gotoh: "Paramyxovirus strategies for evading the interferon response."Reviews in Medical Virology. 12. 337-357 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Bin Gotoh: "The STAT2 activation process is a crucial target of Sendai virus C protein for the blockade of alpha interferon signaling."Journal of Virology. 77. 3360-3370 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Bin Gotoh: "The C-terminal half-fragment of the Sendai virus C protein prevents the gamma-activated factor from binding to a gamma-activated sequence site."Virology. 316. 29-40 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 後藤敏: "ウイルスによるインターフェロン誘導の抑制IRF-3の活性化を抑制するウイルス"蛋白質 核酸 酵素. 49. 511-516 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kenji Takeuchi, Takayuki Komatsu, Junko Yokoo, Atsushi Kato, Tatsuo Shioda, Yoshiyuki Nagai, Bin Gotoh.: "Sendai virus C protein physically associates with Stat1."Genes Cells. 6. 545-557 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Bin Gotoh, Takayuki Komatsu, Kenji Takeuchi, Junko Yokoo.: "Paramyxovirus accessory proteins as interferon antagonists."Microbiol.Immunol.. 45. 787-800 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takayuki Komatsu, Kenji Takeuchi, Junko Yokoo, Bin Gotoh.: "Sendai virus C protein impairs both phosphorylation and dephosphorylation processes of Stat1."FEBS Letters. 511. 139-144 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Bin Gotoh, Takayuki Komatsu, Kenji Takauchi, Junko Yokoo.: "Paramyxovirus strategies for evading the interferon response."Reviews in Medical Virology. 12. 337-357 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Bin Gotoh, Kenji Takeuchi, Takayuki Komatsu, Junko Yokoo.: "The STAT2 activation process is a crucial target of Sendai virus C protein for the blockade of alpha interferon signaling."Journal of Virology. 77. 3360-3370 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Bin Gotoh, Takayuki Komatsu, Kenji Takeuchi, Junko Yokoo.: "The C-terminal half-fragment of the Sendai virus C protein prevents the gamma-activated factor from binding to a gamma-activated sequence site."Virology. 316. 29-40 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Bin Gotoh, Takayuki Komatsu, Kenji Takeuchi.: "Virus interference with the host interferon-induction system."Tanpakushitsu Kakusan Koso. 49. 511-516 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 後藤 敏: "ウイルスによるインターフェロン誘導の抑制 IRF-3の活性化を抑制するウイルス"蛋白質 核酸 酵素. 49・4. 511-516 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Bin Gotoh: "The C-terminal half-fragment of the Sendai virus C protein prevents the gamma-activated factor from binding to a gamma-activated sequence site"Virology. 316・1. 29-40 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Bin Gotoh: "The STAT2 activation process is a crucial target of Sendai virus C protein for the blockade of alpha interferon signaling"Journal of Virology. 77・6. 3360-3370 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Bin Gotoh: "Paramyxovirus strategies for evading the interferon response"Reviews in Medical Virology. 12・6. 337-257 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takayuki Komatsu: "Sendai virus C protein impairs both phosphorylation and dephosphorylation processes of Stat1"FEBS Letters. 511・1-3. 139-144 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Bin Gotoh: "Paramyxovirus accessory proteins as interferon antagonists"Microbiol.Immunol.. 45・12. 787-800 (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kenji Takeuchi: "Sendai virus C protein physically associates with Stat1"Genes Cells. 6・6. 545-557 (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] Gotoh, B.et al.: "The STAT2 activation process is a crucial target of Sendai virus C ptotein for the blockade of alpha interferon signaling"Journal of Virology. 77・6. 3360-3370 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Gotoh, B.et al.: "Paramyxovirus strategies for evading the interferon response"Reviews in Medical Virology. 12・6. 337-357 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Komatsu, T., et al.: "Sendai virus C protein impairs both phophorylation and dephosphorylation processes of Stat1"FEBS Letters. 511(1-3). 139-144 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Gotoh, B., et al.: "(minireview)Paramyxovirus accessory proteins as interferon antagonists"Microbiology and Immunology. 45. 787-800 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takeuchi, K., et al.: "Sendai virus C protein physically associates with Stat1"Genes to Cells. 6. 545-557 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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