https://scholars.lib.ntu.edu.tw/handle/123456789/473784
標題: | Inhibition of miR-146a prevents enterovirus-induced death by restoring the production of type i interferon | 作者: | Ho B.-C. Yu I.-S. Lu L.-F. Rudensky A. Chen H.-Y. Tsai C.-W. YIH-LEONG CHANG CHEN-TU WU LUAN-YIN CHANG Shih S.-R. SHU-WHA LIN Lee C.-N. PAN-CHYR YANG SUNG-LIANG YU |
公開日期: | 2014 | 卷: | 5 | 起(迄)頁: | 4344 | 來源出版物: | Nature Communications | 摘要: | There are no antivirals or vaccines available to treat Enterovirus 71 (EV71) infections. Although the type I interferon response, elicited upon virus infection, is critical to establishing host antiviral innate immunity, EV71 fails to induce this response efficiently. Here we provide new insights into potential anti-EV71 therapy by showing that neutralization of EV71-induced miR-146a prevents death in mice by restarting the production of type I interferon. EV71 infection upregulates miR-146a, which targets IRAK1 and TRAF6 involved in TLR signalling and type I interferon production. We further identify AP1 as being responsible for the EV71-induced expression of miR-146a. Surprisingly, knocking out miR-146a or neutralizing virus-induced miR-146a by specific antagomiR restores expressions of IRAK1 and TRAF6, augments IFNβ production, inhibits viral propagation and improves survival in the mouse model. Our results suggest that enterovirus-induced miR-146a facilitates viral pathogenesis by suppressing IFN production and provide a clue to developing preventive and therapeutic strategies for enterovirus infections. ? 2014 Macmillan Publishers Limited. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84896838762&doi=10.1038%2fncomms4344&partnerID=40&md5=37571f4e6b95a7054292481e7fa20234 https://scholars.lib.ntu.edu.tw/handle/123456789/473784 |
ISSN: | 2041-1723 | DOI: | 10.1038/ncomms4344 | SDG/關鍵字: | antagomir; beta interferon; immunoglobulin enhancer binding protein; interferon; interferon regulatory factor 1; interleukin 1 receptor associated kinase 1; microRNA 146a; protein c fos; protein c jun; toll like receptor; transcription factor AP 1; tumor necrosis factor receptor associated factor 6; interferon; interleukin 1 receptor associated kinase; Irak1 protein, mouse; microRNA; Mirn146 microRNA, mouse; tumor necrosis factor receptor associated factor 6; gene expression; immunity; infectious disease; inhibition; mitochondrial DNA; neutralization; pathogenicity; rodent; signal; survival; virus; animal experiment; animal model; article; binding site; controlled study; Coxsackie virus B3; Enterovirus 71; Enterovirus infection; female; human; human cell; immune response; immunohistochemistry; in vitro study; in vivo study; interferon production; lung edema; male; mouse; myositis; nonhuman; promoter region; protein expression; signal transduction; survival; survival rate; upregulation; virus load; virus pathogenesis; animal; antagonists and inhibitors; C57BL mouse; cell death; drug effects; Enterovirus; Enterovirus Infections; genetics; immunology; metabolism; pathogenicity; tumor cell line; Animals; Cell Death; Cell Line, Tumor; Enterovirus; Enterovirus Infections; Female; Humans; Immunohistochemistry; Interferon Type I; Interleukin-1 Receptor-Associated Kinases; Male; Mice; Mice, Inbred C57BL; MicroRNAs; TNF Receptor-Associated Factor 6 |
顯示於: | 病理學科所 |
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