Ubiquitination and proteasomal degradation of interferon regulatory factor-3 induced by Npro from a cytopathic bovine viral diarrhea virus

Zihong Chen, Rene Rijnbrand, Rohit Jangra, Santhana G. Devaraj, Lin Qu, Yinghong Ma, Stanley M. Lemon, Kui Li

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

The pathogenesis of bovine viral diarrhea virus (BVDV) infections is complex and only partly understood. It remains controversial whether interferon is produced in cells infected with cytopathic(cp) BVDVs which do not persist in vivo. We show here that a cpBVDV (NADL strain) does not induce interferon responses in cell culture and blocks induction of interferon-stimulated genes by a super-infecting paramyxovirus. cpBVDV infection causes a marked loss of interferon regulatory factor 3 (IRF-3), a cellular transcription factor that controls interferon synthesis. This is attributed to expression of Npro, but not its protease activity. Npro interacts with IRF-3, prior to its activation by virus-induced phosphorylation, resulting in polyubiquitination and subsequent proteasomal degradation of IRF-3. Thermal inactivation of the E1 ubiquitin-activating enzyme prevents Npro-induced IRF-3 loss. These data suggest that inhibition of interferon production is a shared feature of both ncp and cpBVDVs and provide new insights regarding IRF-3 regulation in pestivirus pathogenesis.

Original languageEnglish (US)
Pages (from-to)277-292
Number of pages16
JournalVirology
Volume366
Issue number2
DOIs
StatePublished - Sep 30 2007
Externally publishedYes

Fingerprint

Interferon Regulatory Factor-3
Bovine Viral Diarrhea Viruses
Ubiquitination
Interferons
Ubiquitin-Activating Enzymes
Pestivirus
Virus Activation
Virus Diseases
Peptide Hydrolases
Transcription Factors
Cell Culture Techniques
Hot Temperature
Phosphorylation
Infection
Genes

Keywords

  • Bovine viral diarrhea virus
  • Innate immunity
  • Interferon regulatory factor-3
  • Interferon-stimulated gene
  • N-terminal protease
  • Pestivirus
  • Retinoic acid inducible gene I
  • Sendai virus
  • Toll-like receptor 3
  • Ubiquitination

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Ubiquitination and proteasomal degradation of interferon regulatory factor-3 induced by Npro from a cytopathic bovine viral diarrhea virus. / Chen, Zihong; Rijnbrand, Rene; Jangra, Rohit; Devaraj, Santhana G.; Qu, Lin; Ma, Yinghong; Lemon, Stanley M.; Li, Kui.

In: Virology, Vol. 366, No. 2, 30.09.2007, p. 277-292.

Research output: Contribution to journalArticle

Chen, Zihong ; Rijnbrand, Rene ; Jangra, Rohit ; Devaraj, Santhana G. ; Qu, Lin ; Ma, Yinghong ; Lemon, Stanley M. ; Li, Kui. / Ubiquitination and proteasomal degradation of interferon regulatory factor-3 induced by Npro from a cytopathic bovine viral diarrhea virus. In: Virology. 2007 ; Vol. 366, No. 2. pp. 277-292.
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