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

ABSTRACT: 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.

SUBMITTER: Runge S

PROVIDER: S-EPMC3990713 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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

Runge Simon S Sparrer Konstantin M J KM Lässig Charlotte C Hembach Katharina K Baum Alina A García-Sastre Adolfo A Söding Johannes J Conzelmann Karl-Klaus KK Hopfner Karl-Peter KP

PLoS pathogens 20140417 4

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 ...[more]

PMID: 24743923

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Dataset Information

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

Publications

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

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