HIF-1 Transcriptionally Regulates Basal Expression of STING to Maintain Cellular Innate Immunity.
J Immunol
; 213(4): 494-505, 2024 Aug 15.
Article
en En
| MEDLINE
| ID: mdl-38967520
ABSTRACT
Stimulator of IFN genes (STING) is a critical component of the innate immune system, playing an essential role in defending against DNA virus infections. 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)α through transcription. Under normal conditions, HIF-1α binds constitutively to the promoter region of STING, actively promoting its transcription. Knocking down HIF-1α 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-1α in maintaining basal STING levels and provide valuable insights into STING-mediated antiviral activities and associated diseases.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Pez Cebra
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Herpesvirus Humano 1
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Subunidad alfa del Factor 1 Inducible por Hipoxia
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Inmunidad Innata
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Proteínas de la Membrana
Idioma:
En
Revista:
J Immunol
Año:
2024
Tipo del documento:
Article