Comparison of the biological and biochemical activities of several members of the alphaherpesvirus ICP0 family of proteins

Roger D. Everett, Chris Boutell, Carol McNair, Louise Grant, Anne Orr

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Immediate-early protein ICP0 of herpes simplex virus type 1 (HSV-1) is an E3 ubiquitin ligase of the RING finger class that is required for efficient lytic infection and reactivation from latency. Other alphaherpesviruses also express ICP0-related RING finger proteins, but these have limited homology outside the core RING domain. Existing evidence indicates that ICP0 family members have similar properties, but there has been no systematic comparison of the biochemical activities and biological functions of these proteins. Here, we describe an inducible cell line system that allows expression of the ICP0-related proteins of bovine herpes virus type 1 (BHV-1), equine herpesvirus type 1 (EHV-1), pseudorabies virus (PRV), and varicella-zoster virus (VZV) and their subsequent functional analysis. We report that the RING domains of all the proteins have E3 ubiquitin ligase activity in vitro. The BHV-1, EHV-1, and PRV proteins complement ICP0-null mutant HSV-1 plaque formation and induce derepression of quiescent HSV-1 genomes to levels similar to those achieved by ICP0 itself. VICP0, the ICP0 expressed by VZV, was found to be extremely unstable, which limited its analysis in this system. We compared the abilities of the ICP0-related proteins to disrupt ND10, to induce degradation of PML and Sp100, to affect key components of the interferon signaling pathway, and to interfere with induction of interferon-stimulated genes. We found that the property that correlated most closely with their biological activities was the ability to preclude the recruitment of cellular ND10 proteins to sites closely associated with incoming HSV-1 genomes and early replication compartments.

Original languageEnglish
Pages (from-to)3476-3487
Number of pages12
JournalJournal of Virology
Volume84
Issue number7
DOIs
Publication statusPublished - Apr 2010

Keywords

  • herpes-simplex-virus
  • immediate-ealy protein
  • interferon promoter activity
  • reading frame-61 protein
  • cellular gene-expression
  • quiescent viral genomes
  • ring finger domain
  • bovine herpesvirus-1
  • pseudorabies virus
  • equine herpesvirus-1

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