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

Taranjit Singh Rai, Mandy Glass, John J. Cole, Mohammad I. Rather, Morgan Marsden, Matthew Neilson, Claire Brock, Ian R. Humphreys, Roger D. Everett, Peter D. Adams

Research output: Contribution to journalArticle

11 Citations (Scopus)
6 Downloads (Pure)

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. Antiviral 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.

Original languageEnglish
Pages (from-to)11673-11683
Number of pages11
JournalNucleic Acids Research
Volume45
Issue number20
Early online date13 Sep 2017
DOIs
Publication statusPublished - 16 Nov 2017

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