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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990713/ https://www.ncbi.nlm.nih.gov/pubmed/24743923 http://dx.doi.org/10.1371/journal.ppat.1004081 |
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author | Runge, Simon Sparrer, Konstantin M. J. Lässig, Charlotte Hembach, Katharina Baum, Alina García-Sastre, Adolfo Söding, Johannes Conzelmann, Karl-Klaus Hopfner, Karl-Peter |
author_facet | Runge, Simon Sparrer, Konstantin M. J. Lässig, Charlotte Hembach, Katharina Baum, Alina García-Sastre, Adolfo Söding, Johannes Conzelmann, Karl-Klaus Hopfner, Karl-Peter |
author_sort | Runge, Simon |
collection | PubMed |
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 | Online Article Text |
id | pubmed-3990713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39907132014-04-21 In Vivo Ligands of MDA5 and RIG-I in Measles Virus-Infected Cells Runge, Simon Sparrer, Konstantin M. J. Lässig, Charlotte Hembach, Katharina Baum, Alina García-Sastre, Adolfo Söding, Johannes Conzelmann, Karl-Klaus Hopfner, Karl-Peter PLoS Pathog Research Article 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. Public Library of Science 2014-04-17 /pmc/articles/PMC3990713/ /pubmed/24743923 http://dx.doi.org/10.1371/journal.ppat.1004081 Text en © 2014 Runge et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Runge, Simon Sparrer, Konstantin M. J. Lässig, Charlotte Hembach, Katharina Baum, Alina García-Sastre, Adolfo Söding, Johannes Conzelmann, Karl-Klaus Hopfner, Karl-Peter In Vivo Ligands of MDA5 and RIG-I in Measles Virus-Infected Cells |
title |
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_short |
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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990713/ https://www.ncbi.nlm.nih.gov/pubmed/24743923 http://dx.doi.org/10.1371/journal.ppat.1004081 |
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