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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.

Original publication

DOI

10.7554/eLife.01535

Type

Journal article

Journal

Elife

Publication Date

18/02/2014

Volume

3

Keywords

EMCV, LGP2, MDA5, RIG-I-like receptors, antiviral immunity, picornavirus, Animals, Antiviral Agents, Cercopithecus aethiops, DEAD-box RNA Helicases, Encephalomyocarditis virus, Gene Expression Regulation, Viral, HEK293 Cells, HeLa Cells, Host-Pathogen Interactions, Humans, Immunity, Innate, Influenza A virus, Interferon-Induced Helicase, IFIH1, Interferons, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutation, RNA Helicases, RNA, Antisense, RNA, Viral, Receptor, Interferon alpha-beta, Signal Transduction, Transfection, Vero Cells, Virus Replication