MicroRNA-548 down-regulates host antiviral response via direct targeting of IFN-λ1

查看全文 作　　者：Yongkui [1,2]Li;Jiajia [1]Xie;Xiupeng [1]Xu;Jun [1]Wang;Fang [1]Ao;Yushun [1]Wan;Ying [1]Zhu

机构地区：[1]The State Key Laboratory of Virology and College of Life Sciences,Wuhan University,Wuhan 430072,China;[2]Wuhan Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China

出　　处：《Protein & Cell》索引2013年第4卷第2期,共12页

基　　金：supported by research grants from the National Basic Research Program(973 Program)(Nos.2013CB911102,and 2009CB522506);National Mega Project on Major Infectious Diseases Prevention(2012ZX10004503);Na-tional Natural Science Foundation of China(Grant No.81271821). 摘　　要：Interferon(IFN)-mediated pathways are a crucial part of the cellular response against viral infection.Type III IFNs,which include IFN-λ1,2 and 3,mediate antiviral responses similar to Type I IFNs via a distinct receptor complex.IFN-λ1 is more effective than the other two members.Transcription of IFN-λ1 requires activation of IRF3/7 and nuclear factor-kappa B(NF-κB),similar to the transcriptional mechanism of Type I IFNs.Using reporter assays,we discovered that viral infection in-duced both IFN-λ1 promoter activity and that of the 3′-untranslated region(UTR),indicating that IFN-λ1 expression is also regulated at the post-transcriptional level.After analysis with microRNA(miRNA)prediction programs and 3′UTR targeting site assays,the miR-NA-548 family,including miR-548b-5p,miR-548c-5p,miR-548i,miR-548j,and miR-548n,was identified to target the 3′UTR of IFN-λ1.Further study demonstrated that miRNA-548 mimics down-regulated the expression of IFN-λ1.In contrast,their inhibitors,the complemen-tary RNAs,enhanced the expression of IFN-λ1 and IFN-stimulated genes.Furthermore,miRNA-548 mimics promoted infection by enterovirus-71(EV71)and ve-sicular stomatitis virus(VSV),whereas their inhibitors significantly suppressed the replication of EV71 and VSV.Endogenous miRNA-548 levels were suppressed during viral infection.In conclusion,our results sug-gest that miRNA-548 regulates host antiviral response via direct targeting of IFN-λ1,which may offer a poten-tial candidate for antiviral therapy. 关键词：microRNA-548 interferon-λ1 viral infec-tion antiviral response

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MicroRNA-548 down-regulates host antiviral response via direct targeting of IFN-λ1

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