The SARS-CoV-2 protein ORF3c is a mitochondrial modulator of innate immunity.
Immunology
Microbiology
Molecular biology
Proteomics
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
17 Nov 2023
17 Nov 2023
Historique:
received:
12
12
2022
revised:
06
08
2023
accepted:
25
09
2023
medline:
20
10
2023
pubmed:
20
10
2023
entrez:
20
10
2023
Statut:
epublish
Résumé
The SARS-CoV-2 genome encodes a multitude of accessory proteins. Using comparative genomic approaches, an additional accessory protein, ORF3c, has been predicted to be encoded within the ORF3a sgmRNA. Expression of ORF3c during infection has been confirmed independently by ribosome profiling. Despite ORF3c also being present in the 2002-2003 SARS-CoV, its function has remained unexplored. Here we show that ORF3c localizes to mitochondria, where it inhibits innate immunity by restricting IFN-β production, but not NF-κB activation or JAK-STAT signaling downstream of type I IFN stimulation. We find that ORF3c is inhibitory after stimulation with cytoplasmic RNA helicases RIG-I or MDA5 or adaptor protein MAVS, but not after TRIF, TBK1 or phospho-IRF3 stimulation. ORF3c co-immunoprecipitates with the antiviral proteins MAVS and PGAM5 and induces MAVS cleavage by caspase-3. Together, these data provide insight into an uncharacterized mechanism of innate immune evasion by this important human pathogen.
Identifiants
pubmed: 37860693
doi: 10.1016/j.isci.2023.108080
pii: S2589-0042(23)02157-0
pmc: PMC10583119
doi:
Types de publication
Journal Article
Langues
eng
Pagination
108080Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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