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.
Xiaoyuan Lin  1 ,  Beibei Fu  1 ,  Songna Yin  2 ,  Zhifeng Li  3 ,  Huawen Liu  4 ,  Haiwei Zhang  5 ,  Na Xing  6 ,  Yu Wang  7 ,  Weiwei Xue  8 ,  Yan Xiong  1 ,  Shanfu Zhang  1 ,  Qingting Zhao  1 ,  Shiyao Xu  1 ,  Jing Zhang  9 ,  Peihui Wang  9 ,  Weiqi Nian  5 ,  Xingsheng Wang  10 ,  Haibo Wu  1
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.
PMID: 33723527 DOI: 10.1016/j.isci.2021.102293
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.