Type I IFN-Inducible Downregulation of MicroRNA-27a Feedback Inhibits Antiviral Innate Response by Upregulating Siglec1/TRIM27

J Immunol. 2016 Feb 1;196(3):1317-26. doi: 10.4049/jimmunol.1502134. Epub 2015 Dec 23.


Upon recognition of viral components by pattern recognition receptors, including TLRs and retinoic acid-inducible gene I-like helicases, cells are activated to produce type I IFN, which plays key roles in host antiviral innate immune response. However, excessive IFN production may induce immune disorders, and the mechanisms responsible for the regulation of type I IFN production have attracted much attention. Furthermore, type I IFN activates the downstream IFN/JAK/STAT pathway to modulate expression of a set of genes against viral infection, but whether these genes can feedback regulate type I IFN production is poorly understood. In this study, by screening the microRNAs modulated by viral infection in macrophages, we identified that microRNA (miR)-27a was significantly downregulated via the IFN/JAK/STAT1/runt-related transcription factor 1 pathway. Inducible downregulation of miR-27a, in turn, negatively regulated vesicular stomatitis virus-triggered type I IFN production, thus promoting vesicular stomatitis virus replication in macrophages. Mechanistically, we found that miR-27a directly targeted sialic acid-binding Ig-like lectin (Siglec)1 and E3 ubiquitin ligase tripartite motif-containing protein 27 (TRIM27), both of which were previously verified as negative regulators of type I IFN production. Furthermore, we constructed "Sponge" transgenic mice against miR-27a expression and found that Siglec1 and TRIM27 expression were elevated whereas type I IFN production was inhibited and viral replication was aggregated in vivo. Therefore, type I IFN-induced downregulation of miR-27a can upregulate Siglec1 and TRIM27 expression, feedback inhibiting type I IFN production in antiviral innate response. Our study outlines a new negative way to feedback regulate type I IFN production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / immunology
  • Down-Regulation
  • Enzyme-Linked Immunosorbent Assay
  • Feedback, Physiological / physiology
  • Humans
  • Immunity, Innate / immunology
  • Immunoblotting
  • Immunoprecipitation
  • Interferon Type I / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / immunology*
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / immunology
  • Oligonucleotide Array Sequence Analysis
  • RNA Interference
  • RNA, Small Interfering
  • Real-Time Polymerase Chain Reaction
  • Rhabdoviridae Infections / immunology*
  • Rhabdoviridae Infections / metabolism
  • Sialic Acid Binding Ig-like Lectin 1 / biosynthesis*
  • Sialic Acid Binding Ig-like Lectin 1 / immunology
  • Transfection
  • Ubiquitin-Protein Ligases
  • Up-Regulation
  • Vesiculovirus / immunology


  • DNA-Binding Proteins
  • Interferon Type I
  • MicroRNAs
  • Mirn27 microRNA, mouse
  • Nuclear Proteins
  • RNA, Small Interfering
  • Sialic Acid Binding Ig-like Lectin 1
  • Siglec1 protein, mouse
  • Trim27 protein, mouse
  • Ubiquitin-Protein Ligases