The microRNA miR-485 targets host and influenza virus transcripts to regulate antiviral immunity and restrict viral replication

Sci Signal. 2015 Dec 8;8(406):ra126. doi: 10.1126/scisignal.aab3183.

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that are responsible for dynamic changes in gene expression, and some regulate innate antiviral responses. Retinoic acid-inducible gene I (RIG-I) is a cytosolic sensor of viral RNA; RIG-I activation induces an antiviral immune response. We found that miR-485 of the host was produced in response to viral infection and targeted RIG-I mRNA for degradation, which led to suppression of the antiviral response and enhanced viral replication. Thus, inhibition of the expression of mir-485 markedly reduced the replication of Newcastle disease virus (NDV) and the H5N1 strain of influenza virus in mammalian cells. Unexpectedly, miR-485 also bound to the H5N1 gene PB1 (which encodes an RNA polymerase required for viral replication) in a sequence-specific manner, thereby inhibiting replication of the H5N1 virus. Furthermore, miR-485 exhibited bispecificity, targeting RIG-I in cells with a low abundance of H5N1 virus and targeting PB1 in cells with increased amounts of the H5N1 virus. These findings highlight the dual role of miR-485 in preventing spurious activation of antiviral signaling and restricting influenza virus infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / biosynthesis
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / immunology
  • Dogs
  • HEK293 Cells
  • Humans
  • Immunity, Innate*
  • Influenza A Virus, H5N1 Subtype / physiology*
  • Influenza, Human / genetics
  • Influenza, Human / immunology
  • Influenza, Human / metabolism*
  • Madin Darby Canine Kidney Cells
  • MicroRNAs / genetics
  • MicroRNAs / immunology
  • MicroRNAs / metabolism*
  • RNA, Viral / biosynthesis*
  • RNA, Viral / genetics
  • RNA, Viral / immunology
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Viral Proteins / genetics
  • Viral Proteins / immunology
  • Viral Proteins / metabolism
  • Virus Replication / physiology*

Substances

  • MIRN485 microRNA, human
  • MicroRNAs
  • RNA, Viral
  • Viral Proteins
  • influenza virus polymerase basic protein 1
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases