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Journal of Virology, December 2006, p. 11723-11732, Vol. 80, No. 23
0022-538X/06/$08.00+0     doi:10.1128/JVI.01145-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The NPro Product of Bovine Viral Diarrhea Virus Inhibits DNA Binding by Interferon Regulatory Factor 3 and Targets It for Proteasomal Degradation{triangledown}

Louise Hilton,1 Kartykayan Moganeradj,1 Gang Zhang,2 Yun-Hsiang Chen,3 Richard E. Randall,3 John W. McCauley,2,{dagger} and Stephen Goodbourn1*

Division of Basic Medical Sciences, St. George's, University of London, London SW17 0RE, United Kingdom,1 Institute for Animal Health, Compton Laboratory, Compton, Newbury, Berkshire RG20 7NN, United Kingdom,2 Biomolecular Sciences Building, School of Biology, University of St. Andrew's, North Haugh, St. Andrews, KY16 9ST, United Kingdom3

Received 2 June 2006/ Accepted 4 September 2006

Bovine viral diarrhea virus (BVDV) is a pestivirus that can establish a persistent infection in the developing fetus and has the ability to disable the production of type I interferon. In this report, we extend our previous observations that BVDV encodes a protein able to specifically block the activity of interferon regulatory factor 3 (IRF-3), a transcription factor essential for interferon promoter activation, by demonstrating that this is a property of the N-terminal protease fragment (NPro) of the BVDV polyprotein. Although BVDV infections cause relocalization of cellular IRF-3 from the cytoplasm to the nucleus early in infection, NPro blocks IRF-3 from binding to DNA. NPro has the additional property of targeting IRF-3 for polyubiquitination and subsequent destruction by cellular multicatalytic proteasomes. The autoprotease activity of NPro is not required for the inhibition of type I interferon induction or the targeting of IRF-3 for degradation.

* Corresponding author. Mailing address: Division of Basic Medical Sciences, St. George's, University of London, London SW17 0RE, United Kingdom. Phone: 44-20-8725-5942. Fax: 44-20-8725-2992. E-mail: s.goodbourn{at}sgul.ac.uk.

{triangledown} Published ahead of print on 13 September 2006.

{dagger} Present address: Division of Virology, National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom.

Journal of Virology, December 2006, p. 11723-11732, Vol. 80, No. 23
0022-538X/06/$08.00+0     doi:10.1128/JVI.01145-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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