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

Treatment of SARS-CoV-2 ORF8 protein to culture cells derived from macrophage induces IL-17 signaling pathway and promotes the expression of pro-inflammatory cytokines. An expression of ORF8 by adenoviral vector in mouse lung causes pneumonia-like disease associated with the cytokine storm characterized by strong expression of pro-inflammatory cytokines. The severity of this respiratory disease is reduced by the treatment of antibody against IL-17 receptor. ORF8 is involved in the induction of cytokine storm by interacting with IL-17 receptor.