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However, the mechanisms governing basal STING regulation remain poorly understood. In this study, we demonstrate that the basal level of STING is critically maintained by hypoxia-inducible factor 1 (HIF-1)\u03b1 through transcription. Under normal conditions, HIF-1\u03b1 binds constitutively to the promoter region of STING, actively promoting its transcription. Knocking down HIF-1\u03b1 results in a decrease in STING expression in multiple cell lines and zebrafish, which in turn reduces cellular responses to synthetic dsDNAs, including cell signaling and IFN production. Moreover, this decrease in STING levels leads to an increase in cellular susceptibility to DNA viruses HSV-1 and pseudorabies virus. These findings unveil a (to our knowledge) novel role of HIF-1\u03b1 in maintaining basal STING levels and provide valuable insights into STING-mediated antiviral activities and associated diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.2400123","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T10:18:03Z","timestamp":1720174683000},"page":"494-505","source":"Crossref","is-referenced-by-count":10,"title":["HIF-1 Transcriptionally Regulates Basal Expression of STING to Maintain Cellular Innate Immunity"],"prefix":"10.1093","volume":"213","author":[{"given":"Chao","family":"Gao","sequence":"first","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health Security, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglu","family":"Xiao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health Security, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdong","family":"Wang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health Security, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7573-1445","authenticated-orcid":false,"given":"Xinxin","family":"Liang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health Security, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Qin","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health Security, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Zhang","sequence":"additional","affiliation":[{"name":"National 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Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhai","family":"Feng","sequence":"additional","affiliation":[{"name":"State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinbo","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China , Qingdao ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Tang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health Security, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of 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