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J. Virol. doi:10.1128/JVI.01145-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. 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

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

^* To whom correspondence should be addressed. Email: s.goodbourn{at}sgul.ac.uk.

	Abstract

Bovine Viral Diarrhea Virus (BVDV) is a Pestivirus that can establish a persistent infection in the developing foetus, 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 relocalisation 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.

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