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 N Barber, Robert D. Wojahn, Curt M. Horvath

Research output: Contribution to journalArticle

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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
Pages (from-to)7252-7260
Number of pages9
JournalJournal of Virology
Volume83
Issue number14
DOIs
StatePublished - Jul 1 2009

Fingerprint

RNA helicases
RNA Helicases
Respirovirus
Antiviral Agents
Human parainfluenza virus 2
Proteins
proteins
Parainfluenza Virus 5
Hendra Virus
Nipah Virus
Mumps virus
Measles virus
RNA Viruses
Nipah virus
Hendra virus
Innate Immunity
Interferons
viruses
Hydrolysis
Adenosine Triphosphate

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Parisien, J. P., Bamming, D., Komuro, A., Ramachandran, A., Rodriguez, J. J., Barber, G. N., ... 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

A shared interface mediates Paramyxovirus interference with antiviral RNA helicases MDA5 and LGP2. / Parisien, Jean Patrick; Bamming, Darja; Komuro, Akihiko; Ramachandran, Aparna; Rodriguez, Jason J.; Barber, Glen N; Wojahn, Robert D.; Horvath, Curt M.

In: Journal of Virology, Vol. 83, No. 14, 01.07.2009, p. 7252-7260.

Research output: Contribution to journalArticle

Parisien, JP, Bamming, D, Komuro, A, Ramachandran, A, Rodriguez, JJ, Barber, GN, Wojahn, RD & Horvath, CM 2009, 'A shared interface mediates Paramyxovirus interference with antiviral RNA helicases MDA5 and LGP2', Journal of Virology, vol. 83, no. 14, pp. 7252-7260. https://doi.org/10.1128/JVI.00153-09
Parisien, Jean Patrick ; Bamming, Darja ; Komuro, Akihiko ; Ramachandran, Aparna ; Rodriguez, Jason J. ; Barber, Glen N ; Wojahn, Robert D. ; Horvath, Curt M. / A shared interface mediates Paramyxovirus interference with antiviral RNA helicases MDA5 and LGP2. In: Journal of Virology. 2009 ; Vol. 83, No. 14. pp. 7252-7260.
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