{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T23:43:10Z","timestamp":1792539790991,"version":"4.5.0"},"reference-count":55,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Stimulator of interferon genes (STING) is a pivotal innate immune adaptor, and its functions during DNA virus infections have been extensively documented. However, its homeostatic regulation is not well understood. Our study demonstrates that Unc\u201093 homolog B1\u00a0(UNC93B1) is a crucial checker for STING to prevent hyperactivation. Ectopic expression of UNC93B1 attenuates <jats:italic>IFN\u2010\u03b2<\/jats:italic> promoter activity and the transcriptions of <jats:italic>IFN\u2010\u03b2, ISG54<\/jats:italic>, and <jats:italic>ISG56<\/jats:italic> genes. Moreover, UNC93B1 also blocks the IRF3 nuclear translocation induced by ectopic expression of both cyclic GMP\u2010AMP\u00a0synthase (cGAS) and STING and reduces the stability of STING by facilitating its autophagy\u2013lysosome degradation, which can be reversed by lysosome inhibitors. Mechanistically, UNC93B1 interacts with STING and suppresses STING\u2010activated downstream signaling by delivering STING to the lysosomes for degradation, depending on its trafficking capability. <jats:italic>UNC93B1<\/jats:italic> knockout\u00a0in human embryonic kidney 293T\u00a0cells facilitates <jats:italic>IFN\u2010\u03b2<\/jats:italic> promoter activity, <jats:italic>IFN\u2010\u03b2, ISG54<\/jats:italic>, and <jats:italic>ISG56<\/jats:italic> transcriptions, and IRF3 nuclear translocation induced by ectopic expression of cGAS and STING. Infected with herpes simplex virus\u20101 (HSV\u20101), UNC93B1 knockdown BJ cells or primary peritoneal macrophages from <jats:italic>Unc93b1<\/jats:italic>\u2010deficient (<jats:italic>Unc93b1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) mice show enhanced <jats:italic>IFN\u2010\u03b2, ISG54<\/jats:italic>, and <jats:italic>ISG56<\/jats:italic> transcriptions, TBK1 phosphorylation, and reduced STING degradation and viral replication. In addition, <jats:italic>Unc93b1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>\u00a0mice exhibit higher <jats:italic>IFN\u2010\u03b2, ISG54<\/jats:italic>, and <jats:italic>ISG56<\/jats:italic> transcriptions and lower mortality upon HSV\u20101 infection in vivo. Collectively, these findings demonstrate that UNC93B1 attenuates the cGAS\u2013STING signaling pathway by targeting STING for autophagy\u2013lysosome degradation and provide novel insights into the function of UNC93B1 in antiviral innate immunity.<\/jats:p>","DOI":"10.1002\/jmv.27860","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T02:16:00Z","timestamp":1652753760000},"page":"4490-4501","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["UNC93B1 attenuates the cGAS\u2013STING signaling pathway by targeting STING for autophagy\u2013lysosome degradation"],"prefix":"10.1002","volume":"94","author":[{"given":"Huifang","family":"Zhu","sequence":"first","affiliation":[{"name":"Neonatal\/Pediatric Intensive Care Unit, Children's Medical Center First Affiliated Hospital of Gannan Medical University Ganzhou 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