Murine coronavirus induces type I interferon in oligodendrocytes through recognition by RIG-I and MDA5

J Virol. 2010 Jul;84(13):6472-82. doi: 10.1128/JVI.00016-10. Epub 2010 Apr 28.


The murine coronavirus mouse hepatitis virus (MHV) induced the expression of type I interferon (alpha/beta interferon [IFN-alpha/beta]) in mouse oligodendrocytic N20.1 cells. This induction is completely dependent on virus replication, since infection with UV light-inactivated virus could no longer induce IFN-alpha/beta. We show that MHV infection activated both transcription factors, the IFN regulatory factor 3 (IRF-3) and nuclear factor kappaB (NF-kappaB), as evidenced by phosphorylation and nuclear translocation of IRF-3 and an increased promoter binding activity for IRF-3 and NF-kappaB. Furthermore, the cytoplasmic pattern recognition receptor retinoic acid-inducible gene I (RIG-I) was induced by MHV infection. Knockdown of RIG-I by small interfering RNAs blocked the activation of IRF-3 and subsequent IFN-alpha/beta production induced by MHV infection. Knockdown of another cytoplasmic receptor, the melanoma-differentiation-associated gene 5 (MDA5), by small interfering RNAs also blocked IFN-beta induction. These results demonstrate that MHV is recognized by both RIG-I and MDA5 and induces IFN-alpha/beta through the activation of the IRF-3 signaling pathway. However, knockdown of RIG-I only partially blocked NF-kappaB activity induced by MHV infection and inhibition of NF-kappaB activity by a decoy peptide inhibitor had little effect on IFN-alpha/beta production. These data suggest that activation of the NF-kappaB pathway might not play a critical role in IFN-alpha/beta induction by MHV infection in oligodendrocytes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / antagonists & inhibitors
  • DEAD-box RNA Helicases / immunology*
  • Gene Knockdown Techniques
  • Interferon Regulatory Factor-3 / metabolism
  • Interferon Type I / biosynthesis*
  • Interferon-Induced Helicase, IFIH1
  • Mice
  • Murine hepatitis virus / immunology*
  • NF-kappa B / metabolism
  • Oligodendroglia / virology*
  • Phosphorylation
  • Protein Binding
  • Protein Processing, Post-Translational
  • Protein Transport


  • Interferon Regulatory Factor-3
  • Interferon Type I
  • NF-kappa B
  • Ddx58 protein, mouse
  • Ifih1 protein, mouse
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1