IFI207 promotes antiviral responses by modulating STING ubiquitination and degradation.

Aim2-like receptors (ALRs) play crucial roles in innate immune signaling pathways and demonstrate strong positive selection likely driven by pathogens. IFI207, an ALR found in all IMPORTANCE: The innate immune system serves as a first line of defense by utilizing a variety of pattern recognition receptors (PRRs) that detect various nucleic acids generated during virus infection, many of which activate the STING pathway, leading to interferon production. One family of PRRs, the Aim2-like receptors (ALRs), is thought to contribute to innate immunity by this mechanism. However, the Alr locus is highly polymorphic at the sequence and copy number level. We found that at least one member in mice, IFI207, contributes to innate immunity by preventing the degradation of STING that normally occurs after its activation, defining a novel mechanism for sustaining immune response. Several ALRs have been implicated in adipogenesis, autoimmune disease, and inflammation, and identification of the pressures that shaped the genes in the locus is thus important for understanding the biological processes in which the ALRs function.