title: Identification of an LGP2-associated MDA5 agonist in picornavirus-infected cells.
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.
authors.affiliation: Immunobiology Laboratory, Cancer Research UK, London Research Institute, London, United Kingdom.
authors.forename: Safia
authors.initials: S
authors.lastname: Deddouche
authors.forename: Delphine
authors.initials: D
authors.lastname: Goubau
authors.forename: Jan
authors.initials: J
authors.lastname: Rehwinkel
authors.forename: Probir
authors.initials: P
authors.lastname: Chakravarty
authors.forename: Sharmin
authors.initials: S
authors.lastname: Begum
authors.forename: Pierre V
authors.initials: PV
authors.lastname: Maillard
authors.forename: Annabel
authors.initials: A
authors.lastname: Borg
authors.forename: Nik
authors.initials: N
authors.lastname: Matthews
authors.forename: Qian
authors.initials: Q
authors.lastname: Feng
authors.forename: Frank J M
authors.initials: FJ
authors.lastname: van Kuppeveld
authors.forename: Caetano
authors.initials: C
authors.lastname: Reis e Sousa
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D004686:Encephalomyocarditis virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D009980:Influenza A virus / Q000235:genetics / Q000378:metabolism; D000072640:Interferon-Induced Helicase, IFIH1; D007372:Interferons / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D014162:Transfection; D014709:Vero Cells; D014779:Virus Replication
chemical_list: C508032:Ifnar1 protein, mouse; D016372:RNA, Antisense; D012367:RNA, Viral; D053633:Receptor, Interferon alpha-beta; D007372:Interferons; C520569:DHX58 protein, human; C547666:Dhx58 protein, mouse; C452815:IFIH1 protein, human; C510592:Ifih1 protein, mouse; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D020365:RNA Helicases
keywords: EMCV; LGP2; MDA5; RIG-I-like receptors; antiviral immunity; picornavirus