4.7 Article

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

Journal

ISCIENCE
Volume 24, Issue 4, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.isci.2021.102293

Keywords

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Funding

  1. National Natural Science Foundation of China [81970008, 31702205]
  2. Fundamental Research Funds for the Central Universities [2019CDYGZD009, 2020CDJYGRH-1005, 2019CDYGYB005]
  3. Natural Science Foundation of Chongqing, China [cstc2020jcyj-msxmX0460, cstc2020jcyj-bsh0055]
  4. SGC's Rapid Response Funding for COVID-19 [C-0002]

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This study showed that the ORF8 protein of SARS-CoV-2 can induce cytokine storm, with IL-17 signaling pathway playing a crucial role in this process. Treatment with IL17RA antibody can protect mice from ORF8-induced inflammation, providing a potential target for the development of COVID-19 therapeutic drugs.
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.

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