Conserved strategies for pathogen evasion of cGAS–STING immunity

The cyclic GMP–AMP synthase (cGAS)– Stimulator of Interferon Genes (STING) pathway of cytosolic DNA sensing allows mammalian cells to detect and respond to infection with diverse pathogens. Pathogens in turn encode numerous factors that inhibit nearly all steps of cGAS–STING signal transduction. From masking of cytosolic DNA ligands, to post-translational modification of cGAS and STING, and degradation of the nucleotide second messenger 2′3′-cGAMP, pathogens have evolved convergent mechanisms to evade cGAS–STING sensing. Here we examine pathogen inhibitors of innate immunity in the context of newly discovered regulatory features controlling cellular cGAS–STING activation. Comparative analysis of these strategies provides insight into mechanisms of action and suggests aspects of cGAS–STING regulation and immune evasion that remain to be discovered.