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

Everett, R.D., Boutell, C., McNair, C., Grant, L. and Orr, A. (2010) Comparison of the biological and biochemical activities of several members of the alphaherpesvirus ICP0 family of proteins. Journal of Virology, 84(7), pp. 3476-3487. (doi: 10.1128/JVI.02544-09) (PMID:20106921) (PMCID:PMC2838103)

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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 of 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 de-repression of quiescent HSV-1 genomes to extents similar to those achieved by ICP0 itself. VICP0 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, induce degradation of PML and Sp100, to affect key components of the interferon signalling 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Everett, Professor Roger and Orr, Mrs Anne and McNair, Dr Carol and Boutell, Dr Chris and Grant, Dr Louise
Authors: Everett, R.D., Boutell, C., McNair, C., Grant, L., and Orr, A.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
Q Science > QH Natural history > QH301 Biology
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Centre for Virus Research
Journal Name:Journal of Virology
Journal Abbr.:J. Virol.
Publisher:American Society for Microbiology
ISSN:0022-538X
ISSN (Online):1098-5514
Published Online:27 January 2010

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656521The role of ubiquitin and ubiquitin-like proteins during viral infectionChris BoutellMedical Research Council (MRC)MC_UU_12014/5MVLS III - CENTRE FOR VIRUS RESEARCH