MORC3, a component of PML nuclear bodies, has a role in restricting herpes simplex virus type 1 and human cytomegalovirus

Sloan, E. , Orr, A. and Everett, R. (2016) MORC3, a component of PML nuclear bodies, has a role in restricting herpes simplex virus type 1 and human cytomegalovirus. Journal of Virology, 90(19), pp. 8621-8633. (doi: 10.1128/JVI.00621-16) (PMID:27440897) (PMCID:PMC5021396)

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Abstract

We previously reported that MORC3, a protein associated with promyelocytic leukemia nuclear bodies (PML NBs), is a target of HSV-1 ICP0 mediated degradation. Since it is well known that certain other components of the PML NB complex play an important role during an intrinsic immune response to HSV-1, and are also degraded or inactivated by ICP0, we further investigate here the role of MORC3 during HSV-1 infection. We demonstrate that MORC3 has antiviral activity during HSV-1 infection and that this antiviral role is counteracted by ICP0. In addition, MORC3's antiviral role extends to wild type (wt) HCMV infection as its plaque forming efficiency increased in MORC3 depleted cells. We found that MORC3 is recruited to sites associated with HSV-1 genomes after their entry into the nucleus of an infected cell, and in wt infections this is followed by its association with ICP0 foci prior to its degradation. The RING finger domain of ICP0 was required for degradation of MORC3 and we confirmed that no other HSV-1 protein is required for the loss of MORC3. We also found that MORC3 is required for fully efficient recruitment of PML, Sp100, hDaxx and γH2AX to sites associated with HSV-1 genomes entering the host cell nucleus. This study further unravels the intricate ways in which HSV-1 has evolved to counteract the host immune response and reveals a novel function for MORC3 during the host intrinsic immune response.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Everett, Professor Roger and Orr, Mrs Anne and Sloan, Dr Elizabeth
Authors: Sloan, E., Orr, A., and Everett, R.
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 Microbiology
ISSN:0022-538X
ISSN (Online):1070-6321
Published Online:20 July 2016
Copyright Holders:Copyright © 2016 American Society for Microbiology
First Published:First published in Journal of Virology 90(19): 8621-8633
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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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