Inhibition of PARP1 Dampens Pseudorabies Virus Infection through DNA Damage-Induced Antiviral Innate Immunity.
Animals
Antiviral Agents
/ immunology
Cell Line
DNA Damage
/ immunology
Herpesvirus 1, Suid
/ drug effects
Humans
Immunity, Innate
/ drug effects
Membrane Proteins
/ metabolism
Mice
Nucleotidyltransferases
/ metabolism
Poly (ADP-Ribose) Polymerase-1
/ antagonists & inhibitors
Poly(ADP-ribose) Polymerase Inhibitors
/ pharmacology
Pseudorabies
/ drug therapy
Signal Transduction
/ drug effects
Swine
Virus Replication
/ drug effects
DNA damage
cyclic GMP-AMP synthase
innate immunity
poly(ADP-ribose) polymerase 1
pseudorabies virus
stimulator of interferon genes
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
26 07 2021
26 07 2021
Historique:
pubmed:
27
5
2021
medline:
12
10
2021
entrez:
26
5
2021
Statut:
ppublish
Résumé
Pseudorabies virus (PRV) is the causative pathogen of Aujeszky's disease in pigs. Although vaccination is currently applied to prevent the morbidity of PRV infection, new applications are urgently needed to control this infectious disease. Poly(ADP-ribose) polymerase 1 (PARP1) functions in DNA damage repair. We report here that pharmacological and genetic inhibition of PARP1 significantly influenced PRV replication. Moreover, we demonstrate that inhibition of PARP1 induced DNA damage response and antiviral innate immunity. Mechanistically, PARP1 inhibition-induced DNA damage response resulted in the release of double-stranded DNA (dsDNA) into the cytosol, where dsDNA interacted with cyclic GMP-AMP (cGAMP) synthase (cGAS). cGAS subsequently catalyzed cGAMP production to activate the STING/TBK1/IRF3 innate immune signaling pathway. Furthermore, challenge of mice with PARP1 inhibitor stimulated antiviral innate immunity and protected mice from PRV infection
Identifiants
pubmed: 34037418
doi: 10.1128/JVI.00760-21
pmc: PMC8312877
doi:
Substances chimiques
Antiviral Agents
0
Membrane Proteins
0
Poly(ADP-ribose) Polymerase Inhibitors
0
Poly (ADP-Ribose) Polymerase-1
EC 2.4.2.30
Nucleotidyltransferases
EC 2.7.7.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0076021Subventions
Organisme : Ten Thousand Talents Program for Young Talents
ID : W03070106
Organisme : Outstanding Talents of Henan Agricultural University
ID : 30600773
Organisme : Natural Science Foundation of Henan
ID : 202300410213
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