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

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 enc...

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Main Authors:	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
Format:	Article
Language:	English
Published:	eLife Sciences Publications Ltd 2014-02-01
Series:	eLife
Subjects:	RIG-I-like receptor MDA5 LGP2 picornavirus EMCV antiviral immunity
Online Access:	https://elifesciences.org/articles/01535

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spelling	doaj-663aa2a635a647259cca6a484c5c450c2021-05-04T23:00:15ZengeLife Sciences Publications LtdeLife2050-084X2014-02-01310.7554/eLife.01535Identification of an LGP2-associated MDA5 agonist in picornavirus-infected cellsSafia Deddouche0Delphine Goubau1Jan Rehwinkel2Probir Chakravarty3Sharmin Begum4Pierre V Maillard5Annabel Borg6Nik Matthews7Qian Feng8Frank J M van Kuppeveld9Caetano Reis e Sousa10Immunobiology Laboratory, Cancer Research UK, London Research Institute, London, United KingdomImmunobiology Laboratory, Cancer Research UK, London Research Institute, London, United KingdomImmunobiology Laboratory, Cancer Research UK, London Research Institute, London, United KingdomBioinformatics Laboratory, Cancer Research UK, London Research Institute, London, United KingdomClonal Sequencing Laboratory, Cancer Research UK, London Research Institute, London, United KingdomImmunobiology Laboratory, Cancer Research UK, London Research Institute, London, United KingdomProtein Purification Laboratory, Cancer Research UK, London Research Institute, London, United KingdomClonal Sequencing Laboratory, Cancer Research UK, London Research Institute, London, United KingdomVirology Division, Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, NetherlandsVirology Division, Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, NetherlandsImmunobiology Laboratory, Cancer Research UK, London Research Institute, London, United KingdomThe 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.https://elifesciences.org/articles/01535RIG-I-like receptorMDA5LGP2picornavirusEMCVantiviral immunity
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	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
spellingShingle	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 Identification of an LGP2-associated MDA5 agonist in picornavirus-infected cells eLife RIG-I-like receptor MDA5 LGP2 picornavirus EMCV antiviral immunity
author_facet	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
author_sort	Safia Deddouche
title	Identification of an LGP2-associated MDA5 agonist in picornavirus-infected cells
title_short	Identification of an LGP2-associated MDA5 agonist in picornavirus-infected cells
title_full	Identification of an LGP2-associated MDA5 agonist in picornavirus-infected cells
title_fullStr	Identification of an LGP2-associated MDA5 agonist in picornavirus-infected cells
title_full_unstemmed	Identification of an LGP2-associated MDA5 agonist in picornavirus-infected cells
title_sort	identification of an lgp2-associated mda5 agonist in picornavirus-infected cells
publisher	eLife Sciences Publications Ltd
series	eLife
issn	2050-084X
publishDate	2014-02-01
description	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.
topic	RIG-I-like receptor MDA5 LGP2 picornavirus EMCV antiviral immunity
url	https://elifesciences.org/articles/01535
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Identification of an LGP2-associated MDA5 agonist in picornavirus-infected cells

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