The COX2-PGE(2)-PKA axis suppresses antiviral immunity by inhibiting mtDNA-dependent STING activation.

The COX2-PGE2-PKA axis inhibits mtDNA-dependent STING activation, reducing antiviral immunity during herpes simplex virus type 1 infection.

• Why it matters: Understanding how inflammatory mediators regulate STING activation is crucial because chronic STING activation can cause harmful inflammation, and modulating this pathway could improve antiviral responses.
• What they did: The study used herpes simplex virus type 1 infection as a model and found that the COX2-PGE2-PKA pathway acts as a negative regulator of STING, involving PGE2-induced mitophagy via phosphorylation of STOML2 at Ser29.
• The result: This pathway promotes clearance of damaged mitochondria, decreasing cytosolic mitochondrial DNA and STING activation, which suggests targeting COX2-PGE2-PKA could boost innate antiviral immunity.