Stimulation of the replication of ICP0-null mutant HSV-1 and pp71-deficient HCMV by EBV tegument protein BNRF1

Lu, Y., Orr, A. and Everett, R. D. (2016) Stimulation of the replication of ICP0-null mutant HSV-1 and pp71-deficient HCMV by EBV tegument protein BNRF1. Journal of Virology, 90(21), pp. 9664-9673. (doi: 10.1128/JVI.01224-16) (PMID:27535048) (PMCID:PMC5068519)

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Abstract

It is now well established that several cellular proteins that are components of promyelocytic leukaemia nuclear bodies (PML-NBs, also known as ND10) have restrictive effects on herpesvirus infections that are countered by viral proteins that are either present in the virion particle or are expressed during the earliest stages of infection. For example, herpes simplex virus 1 (HSV-1) immediate-early (IE) protein ICP0 overcomes the restrictive effects of PML-NB components PML, Sp100, hDaxx and ATRX while human cytomegalovirus IE protein IE1 and tegument protein pp71 target PML and Sp100, and hDaxx and ATRX, respectively. The functions of these viral regulatory proteins are in part interchangeable, thus both IE1 and pp71 stimulate the replication of ICP0-null mutant HSV-1, while ICP0 increases plaque formation by pp71-deficient HCMV. Here, we extend these studies by examining proteins that are expressed by Epstein-Barr virus (EBV). We report that EBV tegument protein BNRF1, discovered by others to target the hDaxx/ATRX complex, increases the replication of both ICP0-null mutant HSV-1 and pp71-deficient HCMV. In addition, EBV protein EBNA-LP, which targets Sp100, also augments ICP0-null mutant HSV-1 replication. The combination of these two EBV regulatory proteins had a greater effect than each one individually. These findings enhance the concept that disruption of the functions of PML-NB proteins is important for efficient herpesvirus infections.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Everett, Professor Roger and Orr, Mrs Anne
Authors: Lu, Y., Orr, A., and Everett, R. D.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Journal of Virology
Publisher:American Society for General Microbiology
ISSN:0022-1317
ISSN (Online):1465-2099
Published Online:17 August 2016
Copyright Holders:Copyright © 2016 Lu et al.
First Published:First published in Journal of Virology 90(21):9664-9673
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656501Regulation of the initial stages of herpes simplex virus lytic infection and reactivation from latencyRoger EverettMedical Research Council (MRC)MC_UU_12014/4MVLS III - CENTRE FOR VIRUS RESEARCH