The NPro product of bovine viral diarrhea virus inhibits DNA binding by interferon regulatory factor 3 and targets it for proteasomal degradation

Louise Hilton, Kartykayan Moganeradj, Gang Zhang, Yun-Hsiang Chen, Richard Randall, John W McCauley, Stephen Goodbourn

Research output: Contribution to journalArticleResearchpeer-review

176 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)11723 - 11732
Number of pages10
JournalJournal of Virology
Volume80
Issue number23
Publication statusPublished - 2006
Externally publishedYes

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