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

doi:10.1093/nar/gkx771

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 journal › Article › peer-review

53 Citations (Scopus)

152 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 language	English
Pages (from-to)	11673-11683
Number of pages	11
Journal	Nucleic Acids Research
Volume	45
Issue number	20
Early online date	13 Sept 2017
DOIs	https://doi.org/10.1093/nar/gkx771
Publication status	Published (in print/issue) - 16 Nov 2017

Funding

CRUK [C10652/A16566 to P.D.A.]; NIA [P01 AG031862 to P.D.A.]; UWS Start-up Grant (to T.S.R.); Wellcome Trust Senior Research Fellowship in Basic Biomedical Sciences (to I.H., M.M.); EC FP7 Marie Curie Fellowship [PIEF-GA-2009–251948 to M.G.]; MRC Career Development Fellowship; RCUK MRF Research Fellowship [MRF-149–0001-RG-GLASS]. Funding for open access charge: University of Glasgow. Conflict of interest statement. None declared.

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SDG 3 Good Health and Well-being

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10.1093/nar/gkx771Licence: CC BY

Final Published PDFFinal published version, 2.12 MBLicence: CC BY

Cite this

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

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.",

author = "Rai, \{Taranjit Singh\} and Mandy Glass and Cole, \{John J.\} and Rather, \{Mohammad I.\} and Morgan Marsden and Matthew Neilson and Claire Brock and Humphreys, \{Ian R.\} and Everett, \{Roger D.\} and Adams, \{Peter D.\}",

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AU - Rather, Mohammad I.

AU - Marsden, Morgan

AU - Neilson, Matthew

AU - Brock, Claire

AU - Humphreys, Ian R.

AU - Everett, Roger D.

AU - Adams, Peter D.

PY - 2017/11/16

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AB - 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.

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

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

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