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Sensors for replicating viruses and innate immunity
http://hdl.handle.net/10129/2216
http://hdl.handle.net/10129/221608849f99-a74e-46c5-83f7-96788efbd7cc
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
HirosakiMedJ_59_S52.pdf (508.1 kB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||||
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| 公開日 | 2009-09-18 | |||||||
| タイトル | ||||||||
| タイトル | Sensors for replicating viruses and innate immunity | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| 資源タイプ | ||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||
| 資源タイプ | journal article | |||||||
| 著者 |
Fujita, Takashi
× Fujita, Takashi
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| 著者所属 | ||||||||
| Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University | ||||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | Recent studies show the involvement of cytoplasmic RNA helicase family, RIG-I, MDA5 and LGP2 in antiviral innate immune responses. RIG-I and MDA5 are primarily responsible for the detection of viral infection and triggering activation cascade for type I interferon genes in many cell types. RIG-I consists of N-terminal CAspase Recruitment Domain (CARD) and a domain with signatures of DExD/H box helicase (helicase domain). Functional analyses revealed that the helicase domain detects viral RNA and CARD triggers the activation of downstream signaling cascade, including activation of transcription factors, NF-κB, IRF-3 and IRF-7. RIG-I binds to double stranded (ds)RNA, however it does not simply function as a binding receptor for dsRNA, since RIG-I with disrupted ATP binding site is incapable of signaling. A model is proposed that in the absence of dsRNA, RIG-I forms “closed” conformation and upon binding to dsRNA, it conforms into “open” structure exposing CARD. We produced recombinant RIG-I protein using Baculo virus system and purified it to homogeneity. Biochemical properties, including dsRNA binding activity, ATPase activity and helicase activity, of recombinant RIG-I were investigated. The results suggested that RIG-I requires certain structure of ligand RNA that is specifi c to viral (or non-self) origin. Furthermore, we found evidence that RIG-I conforms a certain structure upon binding to dsRNA in the presence of ATP. These results were consistent with the above model for activation of RIG-I. Furthermore, we observed that RIG-I forms oligomers in virus-infected cells and artifi cial oligomerization of RIG-I CARD mimics virusinduced signaling, resulting in the activation of interferon and other cytokine genes. These results highlight how viral replication in cytoplasm is detected by RIG-I helicase and switch on signal cascades for initial antiviral responses. |
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| 引用 | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | 弘前医学. 59(Suppl.), 2007, p.S52-S57 | |||||||
| 書誌情報 |
弘前医学 巻 59, 号 Supplement, p. S52-S57, 発行日 2007-11-29 |
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| ISSN | ||||||||
| 収録物識別子タイプ | ISSN | |||||||
| 収録物識別子 | 0439-1721 | |||||||
| 書誌レコードID | ||||||||
| 収録物識別子タイプ | NCID | |||||||
| 収録物識別子 | AN00211444 | |||||||
| フォーマット | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | application/pdf | |||||||
| 著者版フラグ | ||||||||
| 出版タイプ | VoR | |||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
| 日本十進分類法 | ||||||||
| 主題Scheme | NDC | |||||||
| 主題 | 491.8 | |||||||
| NIIサブジェクト | ||||||||
| 主題Scheme | Other | |||||||
| 主題 | 基礎医学 | |||||||
| 出版者 | ||||||||
| 出版者 | 弘前大学大学院医学研究科・弘前医学会 | |||||||
| 資源タイプ | ||||||||
| 値 | Article | |||||||
