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Journal of Virology, August 2002, p. 7949-7955, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.7949-7955.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Bunyamwera Bunyavirus Nonstructural Protein NSs Counteracts the Induction of Alpha/Beta Interferon

Friedemann Weber,1 Anne Bridgen,2 John K. Fazakerley,3 Hein Streitenfeld,1 Nina Kessler,1 Richard E. Randall,4 and Richard M. Elliott2*

Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany, and,1 Division of Virology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G11 5JR,2 Laboratory for Clinical and Molecular Virology, University of Edinburgh, Edinburgh EH9 1QH,3 School of Biology Sciences, University of St. Andrews, Fife KY16 9TS, Scotland, United Kingdom4

Received 12 February 2002/ Accepted 9 May 2002

Production of alpha/beta interferons (IFN-{alpha}/ß) in response to viral infection is one of the main defense mechanisms of the innate immune system. Many viruses therefore encode factors that subvert the IFN system to enhance their virulence. Bunyamwera virus (BUN) is the prototype of the Bunyaviridae family. By using reverse genetics, we previously produced a recombinant virus lacking the nonstructural protein NSs (BUNdelNSs) and showed that NSs is a nonessential gene product that contributes to viral pathogenesis. Here we demonstrate that BUNdelNSs is a strong inducer of IFN-{alpha}/ß, whereas in cells infected with the wild-type counterpart expressing NSs (wild-type BUN), neither IFN nor IFN mRNA could be detected. IFN induction by BUNdelNSs correlated with activation of NF-{kappa}B and was dependent on virally produced double-stranded RNA and on the IFN transcription factor IRF-3. Furthermore, both in cultured cells and in mice lacking a functional IFN-{alpha}/ß system, BUNdelNSs replicated to wild-type BUN levels, whereas in IFN-competent systems, wild-type BUN grew more efficiently. These results suggest that BUN NSs is an IFN induction antagonist that blocks the transcriptional activation of IFN-{alpha}/ß in order to increase the virulence of Bunyamwera virus.


* Corresponding author. Mailing address: Institute of Virology, University of Glasgow, Church St., Glasgow G11 5JR, Scotland, United Kingdom. Phone: 44 141 330 4024. Fax: 44 141 337 2236. E-mail: r.elliott{at}vir.gla.ac.uk.


Journal of Virology, August 2002, p. 7949-7955, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.7949-7955.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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