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)
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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 |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Cole, Mr John and Rai, Dr Taranjit and Adams, Professor Peter and Everett, Professor Roger and Glass, Dr Mandy and Rather, Dr Mohammad Iqbal 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 > School of Cancer Sciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
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 |
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