HIF-1 Transcriptionally Regulates Basal Expression of STING to Maintain Cellular Innate Immunity

Area of Science:

• Immunology
• Molecular Biology
• Virology

Background:

• Stimulator of Interferon Genes (STING) is crucial for innate immunity against DNA viruses.
• Mechanisms regulating basal STING levels are not well understood.

Purpose of the Study:

• To investigate the role of hypoxia-inducible factor 1 (HIF-1)α in regulating basal STING expression.
• To elucidate the impact of HIF-1α on STING-mediated antiviral responses.

Main Methods:

• Investigated HIF-1α binding to the STING promoter.
• Utilized knockdown experiments in cell lines and zebrafish.
• Assessed cellular responses to synthetic dsDNAs and viral infections.

Main Results:

• HIF-1α constitutively promotes STING transcription under normal conditions.
• HIF-1α knockdown decreased STING expression, cellular signaling, and IFN production.
• Reduced STING levels increased susceptibility to HSV-1 and pseudorabies virus.

Conclusions:

• HIF-1α is essential for maintaining basal STING levels.
• This regulation impacts cellular antiviral defense against DNA viruses.
• Findings offer insights into STING-mediated immunity and disease.