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

Safia Deddouche, Delphine Goubau, Jan Rehwinkel, Probir Chakravarty, Sharmin Begum, Pierre V Maillard, Annabel Borg, Nik Matthews, Qian Feng, Frank J M van Kuppeveld, Caetano Reis e Sousa

    Research output: Contribution to journalArticleAcademicpeer-review


    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:

    Original languageEnglish
    Article numbere01535
    Number of pages20
    Publication statusPublished - 2014


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