Dual signaling via interferon and DNA damage response elicits entrapment by giant PML nuclear bodies.
PML protein
cytomegalovirus
herpesvirus
infectious disease
intrinsic immunity
microbiology
nuclear bodies
viruses
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
23 03 2022
23 03 2022
Historique:
received:
12
08
2021
accepted:
23
03
2022
pubmed:
24
3
2022
medline:
6
4
2022
entrez:
23
3
2022
Statut:
epublish
Résumé
PML nuclear bodies (PML-NBs) are dynamic interchromosomal macromolecular complexes implicated in epigenetic regulation as well as antiviral defense. During herpesvirus infection, PML-NBs induce epigenetic silencing of viral genomes, however, this defense is antagonized by viral regulatory proteins such as IE1 of human cytomegalovirus (HCMV). Here, we show that PML-NBs undergo a drastic rearrangement into highly enlarged PML cages upon infection with IE1-deficient HCMV. Importantly, our results demonstrate that dual signaling by interferon and DNA damage response is required to elicit giant PML-NBs. DNA labeling revealed that invading HCMV genomes are entrapped inside PML-NBs and remain stably associated with PML cages in a transcriptionally repressed state. Intriguingly, by correlative light and transmission electron microscopy (EM), we observed that PML cages also entrap newly assembled viral capsids demonstrating a second defense layer in cells with incomplete first-line response. Further characterization by 3D EM showed that hundreds of viral capsids are tightly packed into several layers of fibrous PML. Overall, our data indicate that giant PML-NBs arise via combined interferon and DNA damage signaling which triggers entrapment of both nucleic acids and proteinaceous components. This represents a multilayered defense strategy to act in a cytoprotective manner and to combat viral infections.
Identifiants
pubmed: 35319461
doi: 10.7554/eLife.73006
pii: 73006
pmc: PMC8975554
doi:
pii:
Substances chimiques
Antiviral Agents
0
Nuclear Proteins
0
Promyelocytic Leukemia Protein
0
Transcription Factors
0
Interferons
9008-11-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022, Scherer et al.
Déclaration de conflit d'intérêts
MS, CR, GN, CK, AK, RM, FF, SW, AR, ES, PW, TS No competing interests declared
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