Necroptosis does not drive disease pathogenesis in a mouse infective model of SARS-CoV-2 in vivo.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
30 Jan 2024
30 Jan 2024
Historique:
received:
26
02
2023
accepted:
15
01
2024
revised:
08
01
2024
medline:
30
1
2024
pubmed:
30
1
2024
entrez:
29
1
2024
Statut:
epublish
Résumé
Necroptosis, a type of lytic cell death executed by the pseudokinase Mixed Lineage Kinase Domain-Like (MLKL) has been implicated in the detrimental inflammation caused by SARS-CoV-2 infection. We minimally and extensively passaged a single clinical SARS-CoV-2 isolate to create models of mild and severe disease in mice allowing us to dissect the role of necroptosis in SARS-CoV-2 disease pathogenesis. We infected wild-type and MLKL-deficient mice and found no significant differences in viral loads or lung pathology. In our model of severe COVID-19, MLKL-deficiency did not alter the host response, ameliorate weight loss, diminish systemic pro-inflammatory cytokines levels, or prevent lethality in aged animals. Our in vivo models indicate that necroptosis is dispensable in the pathogenesis of mild and severe COVID-19.
Identifiants
pubmed: 38286985
doi: 10.1038/s41419-024-06471-6
pii: 10.1038/s41419-024-06471-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
100Subventions
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : GNT1175011
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : GNT1172929
Informations de copyright
© 2024. The Author(s).
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