鸡cGAS-STING通路通过细胞凋亡发挥不依赖干扰素的抗病毒功能。
The Chicken cGAS-STING Pathway Exerts Interferon-Independent Antiviral Function via Cell Apoptosis.
作者信息
Jiang Sen, Lv Mengjia, Zhang Desheng, Cao Qi, Xia Nengwen, Luo Jia, Zheng Wanglong, Chen Nanhua, Meurens François, Zhu Jianzhong
机构信息
Comparative Medicine Research Institute, Yangzhou University, Yangzhou 225009, China.
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
出版信息
Animals (Basel). 2023 Aug 9;13(16):2573. doi: 10.3390/ani13162573.
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.
最近人们认识到，DNA感应先天性免疫cGAS-STING途径发挥不依赖于干扰素的抗病毒功能；然而，鸡源STING（chSTING）是否以及如何发挥这种不依赖于干扰素的抗病毒活性仍然未知。在此，我们表明chSTING在HEK293细胞和鸡细胞中发挥抗病毒活性，不依赖于干扰素的产生。chSTING能够独立于干扰素触发细胞凋亡和自噬，并且凋亡抑制剂而非自噬抑制剂能够拮抗chSTING的抗病毒功能，这表明凋亡参与了不依赖于干扰素的抗病毒功能。此外，chSTING在IRF7基因敲除的鸡巨噬细胞中失去了其抗病毒功能，这表明IRF7不仅对干扰素的产生至关重要，还参与chSTING的其他活动，如凋亡。总体而言，我们的结果表明chSTING发挥不依赖于干扰素的抗病毒功能，可能是通过凋亡实现的。
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