Title: ORF8 contributes to cytokine storm during SARS-CoV-2 infection by activating IL-17 pathway

Lin, Xiaoyuan; Fu, Beibei; Yin, Songna; Li, Zhifeng; Liu, Huawen; Zhang, Haiwei; Xing, Na; Wang, Yu; Xue, Weiwei; Xiong, Yan; Zhang, Shanfu; Zhao, Qingting; Xu, Shiyao; Zhang, Jing; Wang, Peihui; Nian, Weiqi; Wang, Xingsheng; Wu, Haibo

Recently, COVID-19 caused by the novel coronavirus SARS-CoV-2 has brought great challenges to the world. More and more studies have shown that severe patients may suffer from cytokine storm syndrome; however, there are few studies on its pathogenesis. Here we demonstrated that SARS-CoV-2 coding protein open reading frame 8 (ORF8) acted as a contributing factor to cytokine storm during COVID-19 infection. ORF8 could activate IL-17 signaling pathway and promote the expression of pro-inflammatory factors. Moreover, we demonstrated that treatment of IL17RA antibody protected mice from ORF8-induced inflammation. Our findings are helpful to understand the pathogenesis of cytokine storm caused by SARS-CoV-2, and provide a potential target for the development of COVID-19 therapeutic drugs.