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Journal of Virology, October 2006, p. 9667-9675, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.00822-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Interaction of Bunyamwera Orthobunyavirus NSs Protein with Mediator Protein MED8: a Mechanism for Inhibiting the Interferon Response

Vincent H. J. Léonard ,{ddagger},{dagger} Alain Kohl,,{dagger} Timothy J. Hart,§ and Richard M. Elliott*

Division of Virology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G11 5JR, Scotland, United Kingdom

Received 21 April 2006/ Accepted 30 June 2006

The NSs protein of Bunyamwera virus (Bunyaviridae) is an antiapoptotic interferon antagonist involved in silencing host protein expression by interfering with mRNA synthesis. Here, we show that the ability to inhibit both host transcription and the interferon response is linked to interaction of NSs with the MED8 component of Mediator, a protein complex necessary for mRNA production. The interacting domain on NSs was mapped to the C-terminal region, which contains amino acids conserved among orthobunyavirus NSs proteins. A recombinant virus in which the interacting domain in NSs was deleted had strongly reduced ability to inhibit host protein expression and was unable to inhibit the interferon response. This study provides further information on the mechanisms by which bunyavirus nonstructural proteins are involved in pathogenesis.


* Corresponding author. Present address: Centre for Biomolecular Sciences, University of St. Andrews, North Haugh, St. Andrews, KY16 9ST Fife, Scotland, United Kingdom. Phone: 44 1334 463396. Fax: 44 1334 462595. E-mail: rme1{at}st-andrews.ac.uk.

{ddagger} Present address: Molecular Medicine Program, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905.

{dagger} V.H.J.L. and A.K. contributed equally to this study.

Present address: Centre for Biomolecular Sciences, University of St. Andrews, North Haugh, St. Andrews, KY16 9ST Fife, Scotland, United Kingdom.

§ Present address: Department of Molecular Virology, University of Heidelberg, Im Neuenheimer Feld 345, Heidelberg 69120, Germany.


Journal of Virology, October 2006, p. 9667-9675, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.00822-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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