Details

Autor(en) / Beteiligte

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

Titel

MicroRNA-548 down-regulates host antiviral response via direct targeting of IFN- lambda 1

Ist Teil von

• Protein & cell, 2013-02, Vol.4 (2), p.130-141

Erscheinungsjahr

2013

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Interferon (IFN)-mediated pathways are a crucial part of the cellular response against viral infection. Type III IFNs, which include IFN- lambda 1, 2 and 3, mediate antiviral responses similar to Type I IFNs via a distinct receptor complex. IFN- lambda 1 is more effective than the other two members. Transcription of IFN- lambda 1 requires activation of IRF3/7 and nuclear factor-kappa B (NF- Kappa B), similar to the transcriptional mechanism of Type I IFNs. Using reporter assays, we discovered that viral infection induced both IFN- lambda 1 promoter activity and that of the 3'-untranslated region (UTR), indicating that IFN- lambda 1 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- lambda 1. Further study demonstrated that miRNA-548 mimics down-regulated the expression of IFN- lambda 1. In contrast, their inhibitors, the complementary RNAs, enhanced the expression of IFN- lambda 1 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- lambda 1, which may offer a potential candidate for antiviral therapy.