Borna disease virus 1 induces ferroptosis, contributing to lethal encephalitis.
Ferroptosis
Borna disease virus
/ physiology
Animals
Rats
Rats, Sprague-Dawley
Humans
Neurons
/ virology
Lipid Peroxidation
NF-E2-Related Factor 2
/ metabolism
Borna Disease
/ virology
Reactive Oxygen Species
/ metabolism
Signal Transduction
Amino Acid Transport System y+
/ metabolism
Cyclooxygenase 2
/ metabolism
Microglia
/ virology
Phospholipid Hydroperoxide Glutathione Peroxidase
/ metabolism
Heme Oxygenase-1
/ metabolism
Cell Line
Encephalitis
/ virology
Cells, Cultured
Borna disease virus 1 (BoDV‐1)
Nrf2
encephalitis
ferroptosis
ubiquitin‐proteasome system (UPS)
Journal
Journal of medical virology
ISSN: 1096-9071
Titre abrégé: J Med Virol
Pays: United States
ID NLM: 7705876
Informations de publication
Date de publication:
Oct 2024
Oct 2024
Historique:
revised:
03
09
2024
received:
13
06
2024
accepted:
24
09
2024
medline:
7
10
2024
pubmed:
7
10
2024
entrez:
7
10
2024
Statut:
ppublish
Résumé
Borna disease virus 1 (BoDV-1) is a neurotropic RNA virus that has been linked to fatal BoDV-1 encephalitis (BVE) in humans. Ferroptosis represents a newly recognized kind of programmed cell death that marked by iron overload and lipid peroxidation. Various viral infections are closely related to ferroptosis. However, the link between BoDV-1 infection and ferroptosis, as well as its role in BVE pathogenesis, remains inadequately understood. Herein, we used primary rat cortical neurons, human microglial HMC3 cells, and Sprague‒Dawley rats as models. BoDV-1 infection induced ferroptosis, as ferroptosis characteristics were detected (iron overload, reactive oxygen species buildup, decreased antioxidant capacity, lipid peroxidation, and mitochondrial damage). Analysis via qRT-PCR and Western blot demonstrated that BoDV-1-induced ferroptosis was mediated through Nrf2/HO-1/SLC7a11/GPX4 antioxidant pathway suppression. Nrf2 downregulation was due to BoDV-1 infection promoting Nrf2 ubiquitination and degradation. Following BoDV-1-induced ferroptosis, the PTGS2/PGE2 signaling pathway was activated, and various intracellular lipid peroxidation products and damage-associated molecular patterns were released, contributing to BVE occurrence and progression. More importantly, inhibiting ferroptosis or the ubiquitin‒proteasome system effectively alleviated BVE. Collectively, these findings demonstrate the interaction between BoDV-1 infection and ferroptosis and reveal BoDV-1-induced ferroptosis as an underlying pathogenic mechanism of BVE.
Substances chimiques
NF-E2-Related Factor 2
0
Reactive Oxygen Species
0
Amino Acid Transport System y+
0
Cyclooxygenase 2
EC 1.14.99.1
Phospholipid Hydroperoxide Glutathione Peroxidase
EC 1.11.1.12
SLC7A11 protein, human
0
Heme Oxygenase-1
EC 1.14.14.18
Nfe2l2 protein, rat
0
Ptgs2 protein, rat
EC 1.14.99.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e29945Subventions
Organisme : Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences
ID : 2019PT320002
Organisme : Natural Science Foundation Project of China
ID : 81820108015
Organisme : Chinese Stroke Association Whole Course Management of Cerebrovascular Disease Sailing Fund
Organisme : Chongqing Science and Health Joint Medical Research Project
ID : 2023CCXM003
Organisme : Special Funding Project of Chongqing Yongchuan District Research Platform
ID : YJSJ202135
Organisme : Graduate Innovation Fund of the Fifth Clinical College of Chongqing Medical University
ID : YJSCX202207
Informations de copyright
© 2024 Wiley Periodicals LLC.
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