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

Abstract

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.

• Authors: Priya Luthra, Dengyun Sun, Robert H Silverman, Biao He
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 108 Issue 5 Pg. 2118-23 (Feb 01 2011) ISSN: 1091-6490 [Electronic] United States
• PMID: 21245317 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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