In vivo ligands of MDA5 and RIG-I in measles virus-infected cells.

RIG-I-like receptors (RLRs: RIG-I, MDA5 and LGP2) play a major role in the innate immune response against viral infections and detect patterns on viral RNA molecules that are typically absent from host RNA. Upon RNA binding, RLRs trigger a complex downstream signaling cascade resulting in the expres...

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Autores principales:	Simon Runge, Konstantin M J Sparrer, Charlotte Lässig, Katharina Hembach, Alina Baum, Adolfo García-Sastre, Johannes Söding, Karl-Klaus Conzelmann, Karl-Peter Hopfner
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/543293be775c45319f7265a2d0c778e1
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spelling	oai:doaj.org-article:543293be775c45319f7265a2d0c778e12021-11-18T06:06:41ZIn vivo ligands of MDA5 and RIG-I in measles virus-infected cells.1553-73661553-737410.1371/journal.ppat.1004081https://doaj.org/article/543293be775c45319f7265a2d0c778e12014-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24743923/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374RIG-I-like receptors (RLRs: RIG-I, MDA5 and LGP2) play a major role in the innate immune response against viral infections and detect patterns on viral RNA molecules that are typically absent from host RNA. Upon RNA binding, RLRs trigger a complex downstream signaling cascade resulting in the expression of type I interferons and proinflammatory cytokines. In the past decade extensive efforts were made to elucidate the nature of putative RLR ligands. In vitro and transfection studies identified 5'-triphosphate containing blunt-ended double-strand RNAs as potent RIG-I inducers and these findings were confirmed by next-generation sequencing of RIG-I associated RNAs from virus-infected cells. The nature of RNA ligands of MDA5 is less clear. Several studies suggest that double-stranded RNAs are the preferred agonists for the protein. However, the exact nature of physiological MDA5 ligands from virus-infected cells needs to be elucidated. In this work, we combine a crosslinking technique with next-generation sequencing in order to shed light on MDA5-associated RNAs from human cells infected with measles virus. Our findings suggest that RIG-I and MDA5 associate with AU-rich RNA species originating from the mRNA of the measles virus L gene. Corresponding sequences are poorer activators of ATP-hydrolysis by MDA5 in vitro, suggesting that they result in more stable MDA5 filaments. These data provide a possible model of how AU-rich sequences could activate type I interferon signaling.Simon RungeKonstantin M J SparrerCharlotte LässigKatharina HembachAlina BaumAdolfo García-SastreJohannes SödingKarl-Klaus ConzelmannKarl-Peter HopfnerPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 4, p e1004081 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Simon Runge Konstantin M J Sparrer Charlotte Lässig Katharina Hembach Alina Baum Adolfo García-Sastre Johannes Söding Karl-Klaus Conzelmann Karl-Peter Hopfner In vivo ligands of MDA5 and RIG-I in measles virus-infected cells.
description	RIG-I-like receptors (RLRs: RIG-I, MDA5 and LGP2) play a major role in the innate immune response against viral infections and detect patterns on viral RNA molecules that are typically absent from host RNA. Upon RNA binding, RLRs trigger a complex downstream signaling cascade resulting in the expression of type I interferons and proinflammatory cytokines. In the past decade extensive efforts were made to elucidate the nature of putative RLR ligands. In vitro and transfection studies identified 5'-triphosphate containing blunt-ended double-strand RNAs as potent RIG-I inducers and these findings were confirmed by next-generation sequencing of RIG-I associated RNAs from virus-infected cells. The nature of RNA ligands of MDA5 is less clear. Several studies suggest that double-stranded RNAs are the preferred agonists for the protein. However, the exact nature of physiological MDA5 ligands from virus-infected cells needs to be elucidated. In this work, we combine a crosslinking technique with next-generation sequencing in order to shed light on MDA5-associated RNAs from human cells infected with measles virus. Our findings suggest that RIG-I and MDA5 associate with AU-rich RNA species originating from the mRNA of the measles virus L gene. Corresponding sequences are poorer activators of ATP-hydrolysis by MDA5 in vitro, suggesting that they result in more stable MDA5 filaments. These data provide a possible model of how AU-rich sequences could activate type I interferon signaling.
format	article
author	Simon Runge Konstantin M J Sparrer Charlotte Lässig Katharina Hembach Alina Baum Adolfo García-Sastre Johannes Söding Karl-Klaus Conzelmann Karl-Peter Hopfner
author_facet	Simon Runge Konstantin M J Sparrer Charlotte Lässig Katharina Hembach Alina Baum Adolfo García-Sastre Johannes Söding Karl-Klaus Conzelmann Karl-Peter Hopfner
author_sort	Simon Runge
title	In vivo ligands of MDA5 and RIG-I in measles virus-infected cells.
title_short	In vivo ligands of MDA5 and RIG-I in measles virus-infected cells.
title_full	In vivo ligands of MDA5 and RIG-I in measles virus-infected cells.
title_fullStr	In vivo ligands of MDA5 and RIG-I in measles virus-infected cells.
title_full_unstemmed	In vivo ligands of MDA5 and RIG-I in measles virus-infected cells.
title_sort	in vivo ligands of mda5 and rig-i in measles virus-infected cells.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/543293be775c45319f7265a2d0c778e1
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In vivo ligands of MDA5 and RIG-I in measles virus-infected cells.

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