The NPro product of Bovine Viral Diarrhea Virus inhibits DNA binding by Interferon Regulatory Factor-3 and targets it for proteasomal degradation.

L Hilton, K Moganeradj, G Zhang, Y-H Chen, Richard Edward Randall, J McCauley, S Goodbourn

Research output: Contribution to journalArticlepeer-review

188 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
DOIs
Publication statusPublished - Dec 2006

Keywords

  • NF-KAPPA-B
  • DOUBLE-STRANDED-RNA
  • HEPATITIS-C-VIRUS
  • ANTIVIRAL SIGNALING PROTEIN
  • SWINE-FEVER VIRUS
  • BETA-INTERFERON
  • RIG-I
  • GENE-EXPRESSION
  • INNATE IMMUNITY
  • MEDIATED DEGRADATION

Fingerprint

Dive into the research topics of 'The NPro product of Bovine Viral Diarrhea Virus inhibits DNA binding by Interferon Regulatory Factor-3 and targets it for proteasomal degradation.'. Together they form a unique fingerprint.

Cite this