Activation of IFN-β expression by a viral mRNA through RNase L and MDA5

Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2118-23. doi: 10.1073/pnas.1012409108. Epub 2011 Jan 18.


IFNs play a critical role in innate immunity against viral infections. Melanoma differentiation-associated protein 5 (MDA5), an RNA helicase, is a key component in activating the expression of type I IFNs in response to certain types of viral infection. MDA5 senses noncellular RNA and triggers the signaling cascade that leads to IFN production. Synthetic double-stranded RNAs are known activators of MDA5. Natural single-stranded RNAs have not been reported to activate MDA5, however. We have serendipitously identified a viral mRNA from parainfluenza virus 5 (PIV5) that activates IFN expression through MDA5. We provide evidence that the signaling pathway includes the antiviral enzyme RNase L. The L mRNA of PIV5 activated expression of IFN-β. We have mapped the RNA to a region of 430 nucleotides within the L mRNA of PIV5. Our results indicate that a viral mRNA, with 5'-cap and 3'-poly (A), can activate IFN expression through an RNase L-MDA5 pathway.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Northern
  • Cell Line
  • DEAD-box RNA Helicases / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Endoribonucleases / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunoprecipitation
  • Interferon-Induced Helicase, IFIH1
  • Interferon-beta / genetics*
  • RNA, Messenger / physiology*
  • RNA, Small Interfering
  • RNA, Viral / physiology*
  • Signal Transduction


  • RNA, Messenger
  • RNA, Small Interfering
  • RNA, Viral
  • Interferon-beta
  • Endoribonucleases
  • 2-5A-dependent ribonuclease
  • IFIH1 protein, human
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1