Volume 4 Issue 2
Feb.  2013
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Yongkui Li, Jiajia Xie, Xiupeng Xu, Jun Wang, Fang Ao, Yushun Wan, Ying Zhu. MicroRNA-548 down-regulates host antiviral response via direct targeting of IFN-λ1[J]. Protein&Cell, 2013, 4(2): 130-141. doi: 10.1007/s13238-012-2081-y
Citation: Yongkui Li, Jiajia Xie, Xiupeng Xu, Jun Wang, Fang Ao, Yushun Wan, Ying Zhu. MicroRNA-548 down-regulates host antiviral response via direct targeting of IFN-λ1[J]. Protein&Cell, 2013, 4(2): 130-141. doi: 10.1007/s13238-012-2081-y

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

doi: 10.1007/s13238-012-2081-y
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This work was 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), and National Natural Science Foundation of China (Grant No. 81271821).

  • Received Date: 2012-08-13
  • Rev Recd Date: 2012-10-19
  • 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 induced 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 miRNA-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 complementary RNAs, enhanced the expression of IFN-λ1 and IFN-stimulated genes. Furthermore, miRNA-548 mimics promoted infection by enterovirus-71 (EV71) and vesicular 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 suggest that miRNA-548 regulates host antiviral response via direct targeting of IFN-λ1, which may offer a potential candidate for antiviral therapy.
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