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. 2012 Nov 12;4(2):130–141. doi: 10.1007/s13238-012-2081-y

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

Yongkui Li 12081,22081, Jiajia Xie 12081, Xiupeng Xu 12081, Jun Wang 12081, Fang Ao 12081, Yushun Wan 12081, Ying Zhu 12081,✉
PMCID: PMC4875363  PMID: 23150165

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.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-012-2081-y and is accessible for authorized users.

Keywords: microRNA-548, interferon-λ1, viral infection, antiviral response

Electronic supplementary material

13238_2012_2081_MOESM1_ESM.pdf (67.1KB, pdf)

Supplementary material, approximately 67.1 KB.

Footnotes

These authors contributed equally to the work.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-012-2081-y and is accessible for authorized users.

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