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Elife. 2014 Feb 18;3:e01535. doi: 10.7554/eLife.01535.

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

Author information

1
Immunobiology Laboratory, Cancer Research UK, London Research Institute, London, United Kingdom.

Abstract

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.

KEYWORDS:

EMCV; LGP2; MDA5; RIG-I-like receptors; antiviral immunity; picornavirus

PMID:
24550253
PMCID:
PMC3967861
DOI:
10.7554/eLife.01535
[Indexed for MEDLINE]
Free PMC Article

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