The ND10 complex represses lytic human herpesvirus 6A replication and promotes silencing of the viral genome

Sanyal, A., Wallaschek, N., Glass, M., Flamand, L., Wight, D. J. and Kaufer, B. B. (2018) The ND10 complex represses lytic human herpesvirus 6A replication and promotes silencing of the viral genome. Viruses, 10(8), 401. (doi: 10.3390/v10080401) (PMID:30060604) (PMCID:PMC6115956)

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Abstract

Human herpesvirus 6A (HHV-6A) replicates in peripheral blood mononuclear cells (PBMCs) and various T-cell lines in vitro. Intriguingly, the virus can also establish latency in these cells, but it remains unknown what influences the decision between lytic replication and the latency of the virus. Incoming virus genomes are confronted with the nuclear domain 10 (ND10) complex as part of an intrinsic antiviral response. Most herpesviruses can efficiently subvert ND10, but its role in HHV-6A infection remains poorly understood. In this study, we investigated if the ND10 complex affects HHV-6A replication and contributes to the silencing of the virus genome during latency. We could demonstrate that ND10 complex was not dissociated upon infection, while the number of ND10 bodies was reduced in lytically infected cells. Virus replication was significantly enhanced upon knock down of the ND10 complex using shRNAs against its major constituents promyelocytic leukemia protein (PML), hDaxx, and Sp100. In addition, we could demonstrate that viral genes are more efficiently silenced in the presence of a functional ND10 complex. Our data thereby provides the first evidence that the cellular ND10 complex plays an important role in suppressing HHV-6A lytic replication and the silencing of the virus genome in latently infected cells.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Glass, Dr Mandy
Authors: Sanyal, A., Wallaschek, N., Glass, M., Flamand, L., Wight, D. J., and Kaufer, B. B.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Viruses
Publisher:MDPI
ISSN:1999-4915
ISSN (Online):1999-4915
Published Online:29 July 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Viruses 10(8): 401
Publisher Policy:Reproduced under a Creative Commons License

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