MicroRNA-218 inhibits type I interferon production and facilitates virus immune evasion via targeting RIG-I

Biotechnol Appl Biochem. 2020 May;67(3):396-403. doi: 10.1002/bab.1882. Epub 2020 Jan 15.

Abstract

The host protective immunity against viral infection requires the effective detection of viral antigens and the subsequent production of type I interferons (IFNs) by host immune cells. Retinoic acid-inducible gene I (RIG-I) is the crucial signaling element responsible for sensing viral RNA component and initiating the downstream antiviral signaling pathways, leading to the production of type I IFNs. In this work, we identified microRNA-218 (miR-218) as a new virus-induced miRNA that dampens the expression of RIG-I in mouse and human macrophages, leading to the impaired production of type I IFNs. Interfering miR-218 expression rescued RIG-I-mediated antiviral signaling and thus protected macrophages from viral infection. Hence, our results provide new understanding of miRNA-mediated viral immune evasion and may be potentially useful for the treatment of viral infection in the future.

Keywords: RIG-I; macrophages; microRNA; viral infection.

MeSH terms

  • Animals
  • Antiviral Agents / immunology
  • Antiviral Agents / pharmacology*
  • Cells, Cultured
  • DEAD Box Protein 58 / antagonists & inhibitors*
  • DEAD Box Protein 58 / immunology
  • Immune Evasion / drug effects
  • Immune Evasion / immunology
  • Interferon Type I / antagonists & inhibitors*
  • Interferon Type I / biosynthesis
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / virology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / immunology*
  • Microbial Sensitivity Tests
  • Vesiculovirus / drug effects*

Substances

  • Antiviral Agents
  • Interferon Type I
  • MIRN218 microRNA, human
  • MIRN218 microRNA, mouse
  • MicroRNAs
  • Ddx58 protein, mouse
  • DEAD Box Protein 58