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USP22 controls type III interferon signaling and SARS-CoV-2 infection through activation of STING

Pattern recognition receptors (PRRs) and interferons (IFNs) serve as essential antiviral defense against SARS-CoV-2, the causative agent of the COVID-19 pandemic. Type III IFNs (IFN-λ) exhibit cell-type specific and long-lasting functions in auto-inflammation, tumorigenesis, and antiviral defense. H...

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Hauptverfasser: Karlowitz, Rebekka (VerfasserIn) , Stanifer, Megan (VerfasserIn) , Roedig, Jens (VerfasserIn) , Andrieux, Geoffroy (VerfasserIn) , Bojkova, Denisa (VerfasserIn) , Bechtel, Marco (VerfasserIn) , Smith, Sonja (VerfasserIn) , Kowald, Lisa (VerfasserIn) , Schubert, Ralf (VerfasserIn) , Börries, Melanie (VerfasserIn) , Cinatl, Jindrich (VerfasserIn) , Boulant, Steeve (VerfasserIn) , van Wijk, Sjoerd J. L. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 06 August 2022
In: Cell death & disease
Year: 2022, Jahrgang: 13, Heft: 8, Pages: 1-14
ISSN:2041-4889
DOI:10.1038/s41419-022-05124-w
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41419-022-05124-w
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41419-022-05124-w
Volltext
Verfasserangaben:Rebekka Karlowitz, Megan L. Stanifer, Jens Roedig, Geoffroy Andrieux, Denisa Bojkova, Marco Bechtel, Sonja Smith, Lisa Kowald, Ralf Schubert, Melanie Boerries, Jindrich Cinatl, Steeve Boulant and Sjoerd J.L. van Wijk
Beschreibung
Zusammenfassung:Pattern recognition receptors (PRRs) and interferons (IFNs) serve as essential antiviral defense against SARS-CoV-2, the causative agent of the COVID-19 pandemic. Type III IFNs (IFN-λ) exhibit cell-type specific and long-lasting functions in auto-inflammation, tumorigenesis, and antiviral defense. Here, we identify the deubiquitinating enzyme USP22 as central regulator of basal IFN-λ secretion and SARS-CoV-2 infections in human intestinal epithelial cells (hIECs). USP22-deficient hIECs strongly upregulate genes involved in IFN signaling and viral defense, including numerous IFN-stimulated genes (ISGs), with increased secretion of IFN-λ and enhanced STAT1 signaling, even in the absence of exogenous IFNs or viral infection. Interestingly, USP22 controls basal and 2′3′-cGAMP-induced STING activation and loss of STING reversed STAT activation and ISG and IFN-λ expression. Intriguingly, USP22-deficient hIECs are protected against SARS-CoV-2 infection, viral replication, and the formation of de novo infectious particles, in a STING-dependent manner. These findings reveal USP22 as central host regulator of STING and type III IFN signaling, with important implications for SARS-CoV-2 infection and antiviral defense.
Beschreibung:Gesehen am 13.03.2023
Beschreibung:Online Resource
ISSN:2041-4889
DOI:10.1038/s41419-022-05124-w

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