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. 2024 Feb 12;13(2):164. doi: 10.3390/pathogens13020164

Figure 4.

Figure 4

Cytokine storm induced by SARS-CoV-2 proteins (ORF7a, ORF3A, M, and N proteins) mediated by the activation of NF-kB. The structural viral proteins (M and N proteins) and predicted accessory viral proteins (ORF3a and ORF7a proteins) activate the NFκB signaling pathway. Among the 4 viral proteins, ORF7a is the most potent activator of proinflammatory cytokines, whose expression is mediated by NFκB activation. Cytokines such as IL-3, IL-4, and IL-7 were also upregulated by ORF7a. In addition, ORF7a promotes the expression of chemokines. The over-expression of cytokines further activates the NFκB pathway, resulting in the SARS-CoV-induced cytokine storm. * Significantly elevated in COVID-19 patients. ** Overexpression of cytokines further enhances NFκB activation. NFκB: Nuclear factor kappa B; ORF7a: Open-reading frame 7a; ORF3a: Open-reading frame 3a; M: Membrane protein; N: Nucleocapsid protein; IL: Interleukin; TNFα: Tumor necrosis factor-α; IFNβ: Interferon-β; CCL11, 17, 19, 20, 21, 25, 26, 27: Eosinophil chemotactic factors; CXCL9: Chemokine; ↑: Increased or upregulated.