A shared interface mediates Paramyxovirus interference with antiviral RNA helicases MDA5 and LGP2

Jean Patrick Parisien, Darja Bamming, Akihiko Komuro, Aparna Ramachandran, Jason J. Rodriguez, Glen Barber, Robert D. Wojahn, Curt M. Horvath

Research output: Contribution to journalArticle

79 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7252-7260
Number of pages9
JournalJournal of virology
Volume83
Issue number14
DOIs
StatePublished - Jul 2009

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Parisien, J. P., Bamming, D., Komuro, A., Ramachandran, A., Rodriguez, J. J., Barber, G., Wojahn, R. D., & Horvath, C. M. (2009). A shared interface mediates Paramyxovirus interference with antiviral RNA helicases MDA5 and LGP2. Journal of virology, 83(14), 7252-7260. https://doi.org/10.1128/JVI.00153-09