{"id":391,"date":"2022-10-20T15:47:00","date_gmt":"2022-10-20T15:47:00","guid":{"rendered":"https:\/\/boulantlab.com\/?post_type=publications&#038;p=391"},"modified":"2022-10-26T15:53:13","modified_gmt":"2022-10-26T15:53:13","slug":"usp22-controls-type-iii-interferon-signaling-and-sars-cov-2-infection-through-activation-of-sting","status":"publish","type":"publications","link":"https:\/\/boulantlab.com\/publications\/usp22-controls-type-iii-interferon-signaling-and-sars-cov-2-infection-through-activation-of-sting\/","title":{"rendered":"USP22 controls type III interferon signaling and SARS-CoV-2 infection through activation of STING.\ufffc"},"content":{"rendered":"\n<p>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-\u03bb) 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-\u03bb 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-\u03bb and enhanced STAT1 signaling, even in the absence of exogenous IFNs or viral infection. Interestingly, USP22 controls basal and 2&#8217;3&#8242;-cGAMP-induced STING activation and loss of STING reversed STAT activation and ISG and IFN-\u03bb 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.<\/p>\n","protected":false},"featured_media":392,"template":"","_links":{"self":[{"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/publications\/391"}],"collection":[{"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/publications"}],"about":[{"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/types\/publications"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/media\/392"}],"wp:attachment":[{"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/media?parent=391"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}