Abstract
Effective recognition of viral infections and subsequent triggering of antiviral innate immune responses are essential for the host antiviral defense, which is tightly regulated by multiple regulators, including microRNAs (miRNAs). A previous study showed that miR-466l upregulates IL-10 expression in macrophages by antagonizing RNA-binding protein tristetraprolin-mediated IL-10 mRNA degradation. However, the ability of miR-466l to regulate antiviral immune responses remains unknown. Here, we found that interferon-alpha (IFN-α) expression was repressed in Sendai virus (SeV)- and vesicular stomatitis virus (VSV)-infected macrophages and in dendritic cells transfected with miR-466l expression. Moreover, multiple IFN-α species can be directly targeted by miR-466l through their 3′ untranslated region (3′UTR). This study has demonstrated that miR-466l could directly target IFN-α expression to inhibit host antiviral innate immune response.
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Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (no. 81070880), and the China Postdoctoral Science Foundation funded project number 42201. The authors thank Ms Panpan Ma and Tingting Fang for their excellent technical assistance.
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Supplemental Figure 1 Transfection efficiency of miR-466l. Mouse peritoneal macrophages (a), BMDCs (b) and human THP-1 monocytic cell line (c) were transfected with control mimics or miR-466l mimics using INTERFERin (polyplus transfection). After 24 h, total RNA was extracted and miR-466l was detected using qRT-PCR. The primers for miR-466l were RT primer: 5′-GTC GTA TCC AGT GCA GGG TCC GAG GTA TTC GCA CTG GAT ACG ACA ATA TG-3′; qPCR forward primer: 5′-CGT ATA AAT ACA TGC ACA-3′; qPCR reverse primer: 5′-GTG CAG GGT CCG AGG T-3′. Data are shown as mean±s.d. (n=4) of one representative experiment. Similar results were obtained in three independent experiments. **P<0.01. BMDC, bone marrow-derived dendritic cell. (PDF 96 kb)
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Li, Y., Fan, X., He, X. et al. MicroRNA-466l inhibits antiviral innate immune response by targeting interferon-alpha. Cell Mol Immunol 9, 497–502 (2012). https://doi.org/10.1038/cmi.2012.35
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DOI: https://doi.org/10.1038/cmi.2012.35
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