Identification of an LGP2-associated MDA5 agonist in picornavirus-infected cells.

Elife 2014 Feb 18;3:e01535. Epub 2014 Feb 18.

Immunobiology Laboratory, Cancer Research UK, London Research Institute, London, United Kingdom.

The RIG-I-like receptors RIG-I, LGP2, and MDA5 initiate an antiviral response that includes production of type I interferons (IFNs). The nature of the RNAs that trigger MDA5 activation in infected cells remains unclear. Here, we purify and characterise LGP2/RNA complexes from cells infected with encephalomyocarditis virus (EMCV), a picornavirus detected by MDA5 and LGP2 but not RIG-I. We show that those complexes contain RNA that is highly enriched for MDA5-stimulatory activity and for a specific sequence corresponding to the L region of the EMCV antisense RNA. Synthesis of this sequence by in vitro transcription is sufficient to generate an MDA5 stimulatory RNA. Conversely, genomic deletion of the L region in EMCV generates viruses that are less potent at stimulating MDA5-dependent IFN production. Thus, the L region antisense RNA of EMCV is a key determinant of innate immunity to the virus and represents an RNA that activates MDA5 in virally-infected cells. DOI: http://dx.doi.org/10.7554/eLife.01535.001.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967861PMC
http://dx.doi.org/10.7554/eLife.01535DOI Listing
February 2014
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References

(Supplied by CrossRef)
Preference of RIG-I for short viral RNA molecules in infected cells revealed by next-generation sequencing
Baum et al.
Proceedings of the National Academy of Sciences of the United States of America 2010
MDA5 assembles into a polar helical filament on dsRNA
Berke et al.
Proceedings of the National Academy of Sciences of the United States of America 2012

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