The Chicken cGAS–STING Pathway Exerts Interferon-Independent Antiviral Function via Cell Apoptosis

Abstract

It has been recently recognized that the DNA sensing innate immune cGAS-STING pathway exerts an IFN-independent antiviral function; however, whether and how chicken STING (chSTING) exerts such an IFN-independent antiviral activity is still unknown. Here, we showed that chSTING exerts an antiviral activity in HEK293 cells and chicken cells, independent of IFN production. chSTING was able to trigger cell apoptosis and autophagy independently of IFN, and the apoptosis inhibitors, rather than autophagy inhibitors, could antagonize the antiviral function of chSTING, suggesting the involvement of apoptosis in IFN-independent antiviral function. In addition, chSTING lost its antiviral function in IRF7-knockout chicken macrophages, indicating that IRF7 is not only essential for the production of IFN, but also participates in the other activities of chSTING, such as the apoptosis. Collectively, our results showed that chSTING exerts an antiviral function independent of IFN, likely via apoptosis.