2007 Fiscal Year Final Research Report Summary
Basic scientific research for formulating antiviral agents focusing on the immunosuppressive mechanism of virus
| Project/Area Number |
18590062
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
YOKOTA Shin-ichi Sapporo Medical University, School of Medicine, Associate Professor (10325863)
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| Co-Investigator(Kenkyū-buntansha) |
FUJII Nobuhiro Sapporo Medical University, School of Medicine, Professor (90133719)
OKABAYASHI Tamaki Sapporo Medical University, School of Medicine, Instructor (10359995)
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| Project Period (FY) |
2006 – 2007
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| Keywords | viral infection / host immune response / innate immunity / Toll-like receptor / inflammation / negative feedback |
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| Research Abstract |
Measles is a highly contagious viral diseases with fever and rash, particularly in pediatric. Suppression of the host immune response by measles virus (MeV) is a major cause of the high morbidity and mortality rates of acute measles, perhaps due to the role of immunosuppression in secondary infection. In the present study, we propose a novel immunosuppression mechanism of MeV in monocytic cells.
We found that the virus-induced and lipopolysaccharide (LPS)-induced activation of NF-κB and AP-1 was suppressed in monocytic cells infected with MeV, but not in infected epithelial cells. In the infected cells, LPS treatment failed to induce formation of active protein kinase complex containing TAK1, TAB2 and TRAF6, which dissociates from Toll-like receptor complexes containing IRAK1.Ubiquitin-modifying enzyme A20, which is an NF-κB-dependent gene and a host negative feedback regulator of NF-κB, was dramatically upregulated in infected monocytic cells, but not in infected epithelial cells. We demonstrated that MeV phosphoprotein (P protein) expression was necessary and sufficient for the induction ofA20. A negative regulatory motif (ELIE motif) in the A20 promoter was important for transcriptional upregulation of A20 by MeV. And the P protein interacted indirectly with the ELIE motif, and released the suppression of A20 transcription, independent to NF-κB.
Suppression of NF-κB and AP-1 activation, namely immunological silencing, in MeV-infected monocytic cells may be a strategy utilized by MeV to escape rejection and allow the spread of infection throughout the entire body via the blood stream. We consider that P-deficient MeV is a candidate for live-vaccine, which does not cause immunosuppression.
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[Journal Article] Highly-purified Helicobacterpylori LPS preparations induce weak inflammatory reactions and utilize Toll-like receptor 2 complex but not Toll-like receptor 4 complex2007
Author(s)
Yokota, S., Ohnishi, T., Muroi, M., Tanamoto, K., Fujii, N., Amano, K
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Journal Title
FEMS Immunology and Medical Microbiology 51
Pages: 140-148
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cytokine regulation in SARS coronavirus infection compared to other respiratory virus infections2006
Author(s)
Okabyashi, T., Kariwa, H., Yokota, S., Iki, S., Indoh, T., Yokosawa, N., Takashima, I., Tsutsumi, H., Fujii, N
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Journal Title
Journal of Medical Virology 78
Pages: 417-424
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Single nucleotide polymorphisms and functional analysis of MxA promoter region in multipl sclerosis2006
Author(s)
Furuyama, H., Chiba, S., Okabayashi, T., Yokota, S., Nonaka, M., Imai, T., Fujii, N., Matsumoto., H
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Journal Title
Journal of the Neurological Sciences 249
Pages: 153-157
Description
「研究成果報告書概要(欧文)」より
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[Presentation] RSウイルスの自然免疫回避機構2006
Author(s)
岡林 環樹, 横田 伸一, 横沢 紀子, 堤 裕幸, 藤井 暢弘
Organizer
第54回日本ウイルス学会
Place of Presentation
名古屋
Year and Date
20061119-21
Description
「研究成果報告書概要(和文)」より
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[Presentation] Single nucletide polymorphisms and functional analysis of MxA promoter resion in multiple sclerosis2006
Author(s)
Furuyama, H., Chiba, S., Okabayashi, T., Yokota, S., Nonaka, M., Imai, T., Fujii, N., Matsumoto., H
Organizer
The 10th Congress of the EFNS
Place of Presentation
Glasgow
Year and Date
20060902-05
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Helicobacterpylori lipopolysaccharides, which have low endotoxic activity, upregulate Toll-like receptor 4 expression and enhance inflammatory reaction induced by other bacterial lipopolysaccharides2006
Author(s)
Yokota, S., Amano, K., Ohnishi, T., Okabayashi, T., Yokosawa, N., Fujii, N
Organizer
The 26th International Sympodium of the Sapporo Cancer Seminar Foundation
Place of Presentation
Sapporo
Year and Date
20060721-23
Description
「研究成果報告書概要(欧文)」より
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