PMID- 30235352
OWN - NLM
STAT- MEDLINE
DCOM- 20190122
LR  - 20201209
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 14
IP  - 9
DP  - 2018 Sep
TI  - Promyelocytic leukemia (PML) nuclear bodies (NBs) induce latent/quiescent HSV-1 
      genomes chromatinization through a PML NB/Histone H3.3/H3.3 Chaperone Axis.
PG  - e1007313
LID - 10.1371/journal.ppat.1007313 [doi]
LID - e1007313
AB  - Herpes simplex virus 1 (HSV-1) latency establishment is tightly controlled by 
      promyelocytic leukemia (PML) nuclear bodies (NBs) (or ND10), although their exact 
      contribution is still elusive. A hallmark of HSV-1 latency is the interaction 
      between latent viral genomes and PML NBs, leading to the formation of viral 
      DNA-containing PML NBs (vDCP NBs), and the complete silencing of HSV-1. Using a 
      replication-defective HSV-1-infected human primary fibroblast model reproducing 
      the formation of vDCP NBs, combined with an immuno-FISH approach developed to 
      detect latent/quiescent HSV-1, we show that vDCP NBs contain both histone H3.3 
      and its chaperone complexes, i.e., DAXX/ATRX and HIRA complex (HIRA, UBN1, 
      CABIN1, and ASF1a). HIRA also co-localizes with vDCP NBs present in trigeminal 
      ganglia (TG) neurons from HSV-1-infected wild type mice. ChIP and Re-ChIP show 
      that vDCP NBs-associated latent/quiescent viral genomes are chromatinized almost 
      exclusively with H3.3 modified on its lysine (K) 9 by trimethylation, consistent 
      with an interaction of the H3.3 chaperones with multiple viral loci and with the 
      transcriptional silencing of HSV-1. Only simultaneous inactivation of both H3.3 
      chaperone complexes has a significant impact on the deposition of H3.3 on viral 
      genomes, suggesting a compensation mechanism. In contrast, the sole depletion of 
      PML significantly impacts the chromatinization of the latent/quiescent viral 
      genomes with H3.3 without any overall replacement with H3.1. vDCP NBs-associated 
      HSV-1 genomes are not definitively silenced since the destabilization of vDCP NBs 
      by ICP0, which is essential for HSV-1 reactivation in vivo, allows the recovery 
      of a transcriptional lytic program and the replication of viral genomes. 
      Consequently, the present study demonstrates a specific chromatin regulation of 
      vDCP NBs-associated latent/quiescent HSV-1 through an H3.3-dependent HSV-1 
      chromatinization involving the two H3.3 chaperones DAXX/ATRX and HIRA complexes. 
      Additionally, the study reveals that PML NBs are major actors in latent/quiescent 
      HSV-1 H3.3 chromatinization through a PML NB/histone H3.3/H3.3 chaperone axis.
FAU - Cohen, Camille
AU  - Cohen C
AD  - Univ Lyon, Universite Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx 
      DEVweCAN, Institut NeuroMyoGene (INMG), team Chromatin Assembly, Nuclear Domains, 
      Virus, Lyon, France.
FAU - Corpet, Armelle
AU  - Corpet A
AD  - Univ Lyon, Universite Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx 
      DEVweCAN, Institut NeuroMyoGene (INMG), team Chromatin Assembly, Nuclear Domains, 
      Virus, Lyon, France.
FAU - Roubille, Simon
AU  - Roubille S
AD  - Univ Lyon, Universite Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx 
      DEVweCAN, Institut NeuroMyoGene (INMG), team Chromatin Assembly, Nuclear Domains, 
      Virus, Lyon, France.
FAU - Maroui, Mohamed Ali
AU  - Maroui MA
AD  - Univ Lyon, Universite Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx 
      DEVweCAN, Institut NeuroMyoGene (INMG), team Chromatin Assembly, Nuclear Domains, 
      Virus, Lyon, France.
FAU - Poccardi, Nolwenn
AU  - Poccardi N
AD  - Institut de Biologie Integrative de la Cellule (I2BC), Departement de Virologie, 
      Gif-sur-Yvette, France.
FAU - Rousseau, Antoine
AU  - Rousseau A
AD  - Institut de Biologie Integrative de la Cellule (I2BC), Departement de Virologie, 
      Gif-sur-Yvette, France.
AD  - Universite Paris Sud, Centre Hospitalier Universitaire de Bicetre, Service 
      d'Ophthalmologie, Le Kremlin-Bicetre, France.
FAU - Kleijwegt, Constance
AU  - Kleijwegt C
AD  - Univ Lyon, Universite Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx 
      DEVweCAN, Institut NeuroMyoGene (INMG), team Chromatin Assembly, Nuclear Domains, 
      Virus, Lyon, France.
FAU - Binda, Olivier
AU  - Binda O
AD  - Univ Lyon, Universite Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx 
      DEVweCAN, Institut NeuroMyoGene (INMG), team Chromatin Assembly, Nuclear Domains, 
      Virus, Lyon, France.
FAU - Texier, Pascale
AU  - Texier P
AD  - Univ Lyon, Universite Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx 
      DEVweCAN, Institut NeuroMyoGene (INMG), team Chromatin Assembly, Nuclear Domains, 
      Virus, Lyon, France.
FAU - Sawtell, Nancy
AU  - Sawtell N
AD  - Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, Ohio, United States of America.
FAU - Labetoulle, Marc
AU  - Labetoulle M
AD  - Institut de Biologie Integrative de la Cellule (I2BC), Departement de Virologie, 
      Gif-sur-Yvette, France.
AD  - Universite Paris Sud, Centre Hospitalier Universitaire de Bicetre, Service 
      d'Ophthalmologie, Le Kremlin-Bicetre, France.
FAU - Lomonte, Patrick
AU  - Lomonte P
AUID- ORCID: 0000-0001-9248-648X
AD  - Univ Lyon, Universite Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx 
      DEVweCAN, Institut NeuroMyoGene (INMG), team Chromatin Assembly, Nuclear Domains, 
      Virus, Lyon, France.
LA  - eng
GR  - R01 AI093614/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180920
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (CALCOCO2 protein, human)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Co-Repressor Proteins)
RN  - 0 (DAXX protein, human)
RN  - 0 (DNA, Viral)
RN  - 0 (HIRA protein, human)
RN  - 0 (Histone Chaperones)
RN  - 0 (Histones)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Pml protein, mouse)
RN  - 0 (Promyelocytic Leukemia Protein)
RN  - 0 (Transcription Factors)
RN  - 143220-95-5 (PML protein, human)
RN  - EC 3.6.4.12 (ATRX protein, human)
RN  - EC 3.6.4.12 (X-linked Nuclear Protein)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Animals
MH  - Cell Cycle Proteins/metabolism
MH  - Cell Nucleus Structures/metabolism/virology
MH  - Cells, Cultured
MH  - Co-Repressor Proteins
MH  - DNA, Viral/genetics/metabolism
MH  - Female
MH  - Genome, Viral
MH  - Herpesvirus 1, Human/*genetics/*metabolism/pathogenicity
MH  - Histone Chaperones/metabolism
MH  - Histones/metabolism
MH  - Host-Pathogen Interactions
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Molecular Chaperones
MH  - Nuclear Proteins/metabolism
MH  - Promyelocytic Leukemia Protein/deficiency/genetics/*metabolism
MH  - Transcription Factors/metabolism
MH  - Virus Latency/genetics/physiology
MH  - X-linked Nuclear Protein/metabolism
PMC - PMC6168178
COIS- The authors have declared that no competing interests exist.
EDAT- 2018/09/21 06:00
MHDA- 2019/01/23 06:00
PMCR- 2018/09/20
CRDT- 2018/09/21 06:00
PHST- 2018/08/09 00:00 [received]
PHST- 2018/08/31 00:00 [accepted]
PHST- 2018/10/02 00:00 [revised]
PHST- 2018/09/21 06:00 [pubmed]
PHST- 2019/01/23 06:00 [medline]
PHST- 2018/09/21 06:00 [entrez]
PHST- 2018/09/20 00:00 [pmc-release]
AID - PPATHOGENS-D-18-01560 [pii]
AID - 10.1371/journal.ppat.1007313 [doi]
PST - epublish
SO  - PLoS Pathog. 2018 Sep 20;14(9):e1007313. doi: 10.1371/journal.ppat.1007313. 
      eCollection 2018 Sep.