Promyelocytic leukemia (PML) nuclear bodies (NBs) induce latent/quiescent HSV-1 genomes chromatinization through a PML NB/Histone H3.3/H3.3 Chaperone Axis

Autor: Patrick Lomonte, Olivier Binda, Mohamed Ali Maroui, Armelle Corpet, Constance Kleijwegt, Marc Labetoulle, Simon Roubille, Antoine Rousseau, Nolwenn Poccardi, Nancy M. Sawtell, Pascale Texier, Camille Cohen
Přispěvatelé: Bodescot, Myriam, Blanc 2013 - Rôle de la réponse antivirale associée aux PML-NBs dans l'acquisition des profils génomiques latents du virus herpès simplex de type 1 - - VIRUCEPTION2013 - ANR-13-BSV3-0001 - Blanc 2013 - VALID, Development Cancer and Targeted Therapies - - DEVWECAN2010 - ANR-10-LABX-0061 - LABX - VALID, Chromatin Assembly, Nuclear Domains, Virus [Lyon], Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département Virologie (Dpt Viro), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Service d'Ophthalmologie [Le Kremlin-Bicêtre], Université Paris-Sud - Paris 11 (UP11)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Division of Infectious Diseases [Cincinnati, OH, États-Unis], Cincinnati Children's Hospital Medical Center, This work was funded by grants from CNRS (http://www.cnrs.fr), INSERM (https://www.inserm.fr), University Claude Bernard Lyon 1 (https://www.univ-lyon1.fr), French National Agency for Research-ANR (PL, ML, VIRUCEPTION, ANR-13-BSV3- 0001-01, http://www.agence-nationale-recherche.fr), LabEX DEVweCAN (PL, CC, ANR-10-LABX-61, http://www.agence-nationale-recherche.fr), La Ligue contre le cancer and the FINOVI foundation (grant #142690). PL is a CNRS Research Director., ANR-13-BSV3-0001,VIRUCEPTION,Rôle de la réponse antivirale associée aux PML-NBs dans l'acquisition des profils génomiques latents du virus herpès simplex de type 1(2013), ANR-10-LABX-0061,DEVWECAN,Development Cancer and Targeted Therapies(2010), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Sud - Paris 11 (UP11)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
viruses
Cell Cycle Proteins
Herpesvirus 1
Human
Promyelocytic Leukemia Protein
Biochemistry
Histones
Mice
Animal Cells
lcsh:QH301-705.5
Cells
Cultured
Neurons
Viral Genomics
Mice
Inbred BALB C
Mammalian Genomics
biology
Nuclear Proteins
food and beverages
Genomics
Viral Persistence and Latency
Virus Latency
3. Good health
Chromatin
Cell biology
Histone
Lytic cycle
Host-Pathogen Interactions
embryonic structures
Viral Genome
Female
Cellular Types
Cellular Structures and Organelles
Co-Repressor Proteins
Research Article
lcsh:Immunologic diseases. Allergy
X-linked Nuclear Protein
Immunology
Microbial Genomics
Genome
Viral
Genome Complexity
Microbiology
03 medical and health sciences
Histone H3
Death-associated protein 6
Nuclear Bodies
Virology
DNA-binding proteins
Genetics
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
Animals
Humans
Gene silencing
Histone Chaperones
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
Molecular Biology
ATRX
Adaptor Proteins
Signal Transducing
Cell Nucleus
Biology and Life Sciences
Computational Biology
Proteins
Cell Biology
Cell Nucleus Structures
030104 developmental biology
lcsh:Biology (General)
Animal Genomics
Cellular Neuroscience
Chaperone (protein)
DNA
Viral
biology.protein
Parasitology
lcsh:RC581-607
Neuroscience
Molecular Chaperones
Transcription Factors
Zdroj: PLoS Pathogens
PLoS Pathogens, 2018, 14 (9), pp.e1007313. ⟨10.1371/journal.ppat.1007313⟩
PLoS Pathogens, Public Library of Science, 2018, 14 (9), pp.e1007313. ⟨10.1371/journal.ppat.1007313⟩
PLoS Pathogens, Vol 14, Iss 9, p e1007313 (2018)
ISSN: 1553-7366
1553-7374
Popis: 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.
Author summary An understanding of the molecular mechanisms contributing to the persistence of a virus in its host is essential to be able to control viral reactivation and its associated diseases. Herpes simplex virus 1 (HSV-1) is a human pathogen that remains latent in the PNS and CNS of the infected host. The latency is unstable, and frequent reactivations of the virus are responsible for PNS and CNS pathologies. It is thus crucial to understand the physiological, immunological and molecular levels of interplay between latent HSV-1 and the host. Promyelocytic leukemia (PML) nuclear bodies (NBs) control viral infections by preventing the onset of lytic infection. In previous studies, we showed a major role of PML NBs in favoring the establishment of a latent state for HSV-1. A hallmark of HSV-1 latency establishment is the formation of PML NBs containing the viral genome, which we called “viral DNA-containing PML NBs” (vDCP NBs). The genome entrapped in the vDCP NBs is transcriptionally silenced. This naturally occurring latent/quiescent state could, however, be transcriptionally reactivated. Therefore, understanding the role of PML NBs in controlling the establishment of HSV-1 latency and its reactivation is essential to design new therapeutic approaches based on the prevention of viral reactivation.
Databáze: OpenAIRE
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