MicroRNA-548 down-regulates host antiviral response via direct targeting of IFN-λ1.
10.1007/s13238-012-2081-y
- Author:
Yongkui LI
1
;
Jiajia XIE
;
Xiupeng XU
;
Jun WANG
;
Fang AO
;
Yushun WAN
;
Ying ZHU
Author Information
1. The State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
- Publication Type:Journal Article
- MeSH:
3' Untranslated Regions;
Adult;
Antiviral Agents;
pharmacology;
therapeutic use;
Base Sequence;
Down-Regulation;
drug effects;
Female;
Hep G2 Cells;
Hepatitis B, Chronic;
drug therapy;
metabolism;
pathology;
Humans;
Interferon Regulatory Factor-3;
metabolism;
Interferon Regulatory Factor-7;
metabolism;
Interleukins;
antagonists & inhibitors;
genetics;
metabolism;
Leukocytes, Mononuclear;
metabolism;
Male;
MicroRNAs;
metabolism;
Middle Aged;
NF-kappa B;
metabolism;
Poly I-C;
pharmacology;
therapeutic use;
Promoter Regions, Genetic;
RNA Interference;
RNA, Small Interfering;
metabolism
- From:
Protein & Cell
2013;4(2):130-141
- CountryChina
- Language:English
-
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.
