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

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

doi:10.1016/j.isci.2021.102293

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

iScience. 2021 Apr 23;24(4):102293. doi: 10.1016/j.isci.2021.102293. Epub 2021 Mar 9.

Authors

Xiaoyuan Lin¹, Beibei Fu¹, Songna Yin², Zhifeng Li³, Huawen Liu⁴, Haiwei Zhang⁵, Na Xing⁶, Yu Wang⁷, Weiwei Xue⁸, Yan Xiong¹, Shanfu Zhang¹, Qingting Zhao¹, Shiyao Xu¹, Jing Zhang⁹, Peihui Wang⁹, Weiqi Nian⁵, Xingsheng Wang¹⁰, Haibo Wu¹

Affiliations

¹ School of Life Sciences, Chongqing University, Chongqing 401331, China.
² Medical school, Yan'an University, Yan'an, 716000 Shaanxi, China.
³ Chongqing Center for Disease Control and Prevention, Chongqing 400042, China.
⁴ Affiliated Three Gorges Hospital of Chongqing University, Chongqing Three Gorges Central Hospital, Chongqing 404100, China.
⁵ Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China.
⁶ Institut für Virologie, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany.
⁷ Technical Center of Chongqing Customs, Chongqing 401147, China.
⁸ School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China.
⁹ Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
¹⁰ Department of Respiratory Medicine, Affiliated Central Hospital of Chongqing University, Chongqing Emergency Medical Center, Chongqing 400014, China.

Abstract

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 patients with severe COVID-19 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.

Keywords: Biological Sciences; Microbiology; Virology.

Abstract

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