Sensors for replicating viruses and innate immunity
- フォーマット:
- 論文
- 責任表示:
- Fujita, Takashi
- 言語:
- 英語
- 出版情報:
- 弘前大学大学院医学研究科・弘前医学会, 2007-11-29
- 著者名:
- Fujita, Takashi
- 掲載情報:
- 弘前医学
- ISSN:
- 0439-1721
- 巻:
- 59
- 通号:
- Supplement
- 開始ページ:
- S52
- 終了ページ:
- S57
- バージョン:
- publisher
- 概要:
- Recent studies show the involvement of cytoplasmic RNA helicase family, RIG-I, MDA5 and LGP2 inantiviral innate immune responses. RIG-I and MDA5 are primarily responsible for the detection of viral infectionand triggering activation cascade for type I interferon genes in many cell types. RIG-I consists of N-terminalCAspase 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 ofdownstream signaling cascade, including activation of transcription factors, NF-κB, IRF-3 and IRF-7. RIG-I bindsto double stranded (ds)RNA, however it does not simply function as a binding receptor for dsRNA, since RIG-Iwith 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. Biochemicalproperties, including dsRNA binding activity, ATPase activity and helicase activity, of recombinant RIG-I wereinvestigated. The results suggested that RIG-I requires certain structure of ligand RNA that is specifi c to viral (ornon-self) origin. Furthermore, we found evidence that RIG-I conforms a certain structure upon binding to dsRNA inthe presence of ATP. These results were consistent with the above model for activation of RIG-I. Furthermore, weobserved that RIG-I forms oligomers in virus-infected cells and artifi cial oligomerization of RIG-I CARD mimics virusinducedsignaling, resulting in the activation of interferon and other cytokine genes. These results highlight how viralreplication in cytoplasm is detected by RIG-I helicase and switch on signal cascades for initial antiviral responses. 続きを見る
- URL:
- http://hdl.handle.net/10129/2216
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