The chicken cGAS-STING pathway exerts interferon independent antiviral function via cell apoptosis

Abstract

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 both mammalian cells and chicken cells, either with or without the production of IFN. On the other hand, chSTING was able to trigger cell apoptosis and autophagy independently of IFN, and the apoptosis inhibitors instead of autophagy inhibitors could antagonize the antiviral function of chSTING, suggesting the involvement of apoptosis in the 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 the antiviral function independently of IFN, likely via the apoptosis.