Cytoplasmic localized infected cell protein 0 (bICP0) encoded by bovine herpesvirus 1 inhibits β interferon promoter activity and reduces IRF3 (interferon response factor 3) protein levels

Leticia Frizzo da Silva, Natasha Gaudreault, Clinton Jones

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Bovine herpesvirus 1 (BHV-1), an alpha-herpesvirinae subfamily member, establishes a life-long latent infection in sensory neurons. Periodically, BHV-1 reactivates from latency, infectious virus is spread, and consequently virus transmission occurs. BHV-1 acute infection causes upper respiratory track infections and conjunctivitis in infected cattle. As a result of transient immune-suppression, BHV-1 infections can also lead to life-threatening secondary bacterial pneumonia that is referred to as bovine respiratory disease. The infected cell protein 0 (bICP0) encoded by BHV-1 reduces human β-interferon (IFN-β) promoter activity, in part, by inducing degradation of interferon response factor 3 (IRF3) and interacting with IRF7. In contrast to humans, cattle contain three IFN-β genes. All three bovine IFN-β proteins have anti-viral activity: but each IFN-β gene has a distinct transcriptional promoter. We have recently cloned and characterized the three bovine IFN-β promoters. Relative to the human IFN-β promoter, each of the three IFN-β promoters contain differences in the four positive regulatory domains that are required for virus-induced activity. In this study, we demonstrate that bICP0 effectively inhibits bovine IFN-β promoter activity following transfection of low passage bovine cells with interferon response factor 3 (IRF3) or IRF7. A bICP0 mutant that localizes to the cytoplasm inhibits bovine IFN-β promoter activity as efficiently as wt bICP0. The cytoplasmic localized bICP0 protein also induced IRF3 degradation with similar efficiency as wt bICP0. In summary, these studies suggested that cytoplasmic localized bICP0 plays a role in inhibiting the IFN-β response during productive infection.

Original languageEnglish (US)
Pages (from-to)143-149
Number of pages7
JournalVirus Research
Volume160
Issue number1-2
DOIs
StatePublished - Sep 1 2011
Externally publishedYes

Keywords

  • BICP0
  • Bovine herpesvirus 1
  • IRF3
  • β-Interferon

ASJC Scopus subject areas

  • Cancer Research
  • Virology
  • Infectious Diseases

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