Inhibition of miR-146a prevents enterovirus-induced death by restoring the production of type I interferon Journal Article
| Authors: | Ho, B. C.; Yu, I. S.; Lu, L. F. ; Rudensky, A.; Chen, H. Y.; Tsai, C. W.; Chang, Y. L.; Wu, C. T.; Chang, L. Y.; Shih, S. R.; Lin, S. W.; Lee, C. N.; Yang, P. C.; Yu, S. L. |
| Article Title: | Inhibition of miR-146a prevents enterovirus-induced death by restoring the production of type I interferon |
| Abstract: | 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. |
| Keywords: | immunohistochemistry; signal transduction; survival; controlled study; protein expression; survival rate; human cell; promoter region; interferon; nonhuman; mouse; gene expression; animal experiment; animal model; immunoglobulin enhancer binding protein; in vivo study; in vitro study; immune response; binding site; upregulation; rodent; virus load; immunity; pathogenicity; virus; beta interferon; toll like receptor; mitochondrial dna; inhibition; signal; infectious disease; transcription factor ap 1; myositis; antagomir; lung edema; virus pathogenesis; tumor necrosis factor receptor associated factor 6; protein c fos; interferon production; protein c jun; interleukin 1 receptor associated kinase 1; interferon regulatory factor 1; microrna 146a; neutralization; human; male; female; article; coxsackie virus b3; enterovirus 71; enterovirus infection |
| Journal Title: | Nature Communications |
| Volume: | 5 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2014-02-01 |
| Start Page: | 4344 |
| Language: | English |
| DOI: | 10.1038/ncomms4344 |
| PROVIDER: | scopus |
| PUBMED: | 24561744 |
| DOI/URL: | |
| Notes: | Export Date: 2 April 2014 -- Source: Scopus |
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