Regulation of Innate Immune Responses by Bovine Herpesvirus 1 and Infected Cell Protein 0 (bICP0).

Clinton Jones

doi:10.3390/v1020255

Abstract

Bovine herpesvirus 1 (BoHV-1) infected cell protein 0 (bICP0) is an important transcriptional regulatory protein that stimulates productive infection. In transient transfection assays, bICP0 also inhibits interferon dependent transcription. bICP0 can induce degradation of interferon stimulatory factor 3 (IRF3), a cellular transcription factor that is crucial for activating beta interferon (IFN-β) promoter activity. Recent studies also concluded that interactions between bICP0 and IRF7 inhibit trans-activation of IFN-β promoter activity. The C3HC4 zinc RING (really important new gene) finger located near the amino terminus of bICP0 is important for all known functions of bICP0. A recombinant virus that contains a single amino acid change in a well conserved cysteine residue of the C3HC4 zinc RING finger of bICP0 grows poorly in cultured cells, and does not reactivate from latency in cattle confirming that the C3HC4 zinc RING finger is crucial for viral growth and pathogenesis. A bICP0 deletion mutant does not induce plaques in permissive cells, but induces autophagy in a cell type dependent manner. In summary, the ability of bICP0 to stimulate productive infection, and repress IFN dependent transcription plays a crucial role in the BoHV-1 infection cycle.

Highlights

Bovine herpesvirus 1 (BoHV-1) infection can cause conjunctivitis, pneumonia, genital disorders, abortions, and an upper respiratory infection known as bovine respiratory disease (BRD) or “Shipping Fever” [136]
2.1. bICP0 is encoded within immediate early transcript unit 1 (IEtu1)
IE gene expression is stimulated by a virion component, bTIF, which interacts with a cellular transcription factor (Oct-1)

Summary

Introduction

BoHV-1 infection can cause conjunctivitis, pneumonia, genital disorders, abortions, and an upper respiratory infection known as bovine respiratory disease (BRD) or “Shipping Fever” [136]. BoHV-1 initiates BRD by immunosuppressing cattle [24,48,49,50,152], which can lead to pneumonia as a result of secondary bacterial infections. There have been increases in BoHV-1 outbreaks in vaccinated feedlot cattle, which are the result of vaccine strains reactivating from latency [33,66,137,139]. The bICP0 protein has two known functions that are important for stimulating productive infection and promoting viral pathogenesis: stimulating the activity of all viral promoters and inhibiting interferon dependent transcription. These bICP0 functions are the focus of this review

Results and Discussion

Activation of the interferon pathway following infection

Growth properties of bICP0 mutant viruses

Regulation of immune responses by other BoHV-1 genes

Conclusions