A Shared Interface Mediates Paramyxovirus Interference with Antiviral RNA Helicases MDA5 and LGP2
Open Access
- 15 July 2009
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 83 (14), 7252-7260
- https://doi.org/10.1128/jvi.00153-09
Abstract
Diverse members of the Paramyxovirus family of negative-strand RNA viruses effectively suppress host innate immune responses through the actions of their V proteins. The V protein mediates interference with the interferon regulatory RNA helicase MDA5 to avoid cellular antiviral responses. Analysis of the interaction interface revealed the MDA5 helicase C domain as necessary and sufficient for association with V proteins from human parainfluenza virus type 2, parainfluenza virus type 5, measles virus, mumps virus, Hendra virus, and Nipah virus. The identified ∼130-residue region is highly homologous between MDA5 and the related antiviral helicase LGP2, but not RIG-I. Results indicate that the paramyxovirus V proteins can also associate with LGP2. The V protein interaction was found to disrupt ATP hydrolysis mediated by both MDA5 and LGP2. These findings provide a potential mechanistic basis for V protein-mediated helicase interference and identify LGP2 as a second cellular RNA helicase targeted by paramyxovirus V proteins.Keywords
This publication has 32 references indexed in Scilit:
- A Novel Role for Viral-Defective Interfering Particles in Enhancing Dendritic Cell MaturationThe Journal of Immunology, 2006
- Sendai virus defective-interfering genomes and the activation of interferon-betaVirology, 2006
- Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirusProceedings of the National Academy of Sciences of the United States of America, 2006
- Differential roles of MDA5 and RIG-I helicases in the recognition of RNA virusesNature, 2006
- MasterCARD: a priceless link to innate immunityTrends in Molecular Medicine, 2006
- The DEAD-box protein family of RNA helicasesGene, 2006
- The RNA Helicase Lgp2 Inhibits TLR-Independent Sensing of Viral Replication by Retinoic Acid-Inducible Gene-IThe Journal of Immunology, 2005
- Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virusNature, 2005
- VISA Is an Adapter Protein Required for Virus-Triggered IFN-β SignalingMolecular Cell, 2005
- Identification and Characterization of MAVS, a Mitochondrial Antiviral Signaling Protein that Activates NF-κB and IRF3Cell, 2005