Protein & Cell

, Volume 4, Issue 2, pp 130–141

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

  • Yongkui Li
  • Jiajia Xie
  • Xiupeng Xu
  • Jun Wang
  • Fang Ao
  • Yushun Wan
  • Ying Zhu
Research Article

DOI: 10.1007/s13238-012-2081-y

Cite this article as:
Li, Y., Xie, J., Xu, X. et al. Protein Cell (2013) 4: 130. doi:10.1007/s13238-012-2081-y

Abstract

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.

Keywords

microRNA-548 interferon-λ1 viral infection antiviral response 

Supplementary material

13238_2012_2081_MOESM1_ESM.pdf (67 kb)
Supplementary material, approximately 67.1 KB.

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Yongkui Li
    • 1
    • 2
  • Jiajia Xie
    • 1
  • Xiupeng Xu
    • 1
  • Jun Wang
    • 1
  • Fang Ao
    • 1
  • Yushun Wan
    • 1
  • Ying Zhu
    • 1
  1. 1.The State Key Laboratory of Virology and College of Life SciencesWuhan UniversityWuhanChina
  2. 2.Wuhan Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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