Histone chaperone HIRA deposits histone H3.3 onto foreign viral DNA and contributes to anti-viral intrinsic immunity

Rai, T. S., Glass, M., Cole, J. J., Rather, M., Marsden, M., Neilson, M., Brock, C., Humphreys, I. R., Everett, R. D. and Adams, P. D. (2017) Histone chaperone HIRA deposits histone H3.3 onto foreign viral DNA and contributes to anti-viral intrinsic immunity. Nucleic Acids Research, 45(20), pp. 11673-11683. (doi:10.1093/nar/gkx771) (PMID:28981850) (PMCID:PMC5691367)

[img]
Preview
Text
146875.pdf - Published Version
Available under License Creative Commons Attribution.

2MB

Abstract

The HIRA histone chaperone complex deposits histone H3.3 into nucleosomes in a DNA replication- and sequence-independent manner. As herpesvirus genomes enter the nucleus as naked DNA, we asked whether the HIRA chaperone complex affects herpesvirus infection. After infection of primary cells with HSV or CMV, or transient transfection with naked plasmid DNA, HIRA re-localizes to PML bodies, sites of cellular anti-viral activity. HIRA co-localizes with viral genomes, binds to incoming viral and plasmid DNAs and deposits histone H3.3 onto these. Anti-viral interferons (IFN) specifically induce HIRA/PML co-localization at PML nuclear bodies and HIRA recruitment to IFN target genes, although HIRA is not required for IFN-inducible expression of these genes. HIRA is, however, required for suppression of viral gene expression, virus replication and lytic infection and restricts murine CMV replication in vivo. We propose that the HIRA chaperone complex represses incoming naked viral DNAs through chromatinization as part of intrinsic cellular immunity.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Everett, Professor Roger and Adams, Professor Peter and Glass, Dr Mandy and Cole, Mr John and Rather, Dr Mohammad Iqbal and Rai, Dr Taranjit and Neilson, Dr Matthew
Authors: Rai, T. S., Glass, M., Cole, J. J., Rather, M., Marsden, M., Neilson, M., Brock, C., Humphreys, I. R., Everett, R. D., and Adams, P. D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nucleic Acids Research
Publisher:Oxford University Press
ISSN:0305-1048
ISSN (Online):1362-4962
Published Online:13 September 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Nucleic Acids Research 45(20):11673-11683
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
625581Senescence-associated chromatin changes a barrier to tumor progression.Peter AdamsCancer Research UK (CRUK)C10652/A16566ICS - EPIGENETICS