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Journal of Virology, July 2009, p. 7252-7260, Vol. 83, No. 14
0022-538X/09/$08.00+0     doi:10.1128/JVI.00153-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Shared Interface Mediates Paramyxovirus Interference with Antiviral RNA Helicases MDA5 and LGP2{triangledown}

Jean-Patrick Parisien,1 Darja Bamming,1 Akihiko Komuro,1 Aparna Ramachandran,1 Jason J. Rodriguez,1 Glen Barber,2 Robert D. Wojahn,1 and Curt M. Horvath1*

Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208,1 Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 331362

Received 22 January 2009/ Accepted 23 April 2009

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.

* Corresponding author. Mailing address: Pancoe ENH Pavilion, Rm. 4401, 2200 Campus Drive, Evanston, IL 60208. Phone: (847) 491-5530. Fax: (847) 491-4400. E-mail: horvath{at}northwestern.edu

{triangledown} Published ahead of print on 29 April 2009.

Journal of Virology, July 2009, p. 7252-7260, Vol. 83, No. 14
0022-538X/09/$08.00+0     doi:10.1128/JVI.00153-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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