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. 2021 Oct 27;13(11):2165. doi: 10.3390/v13112165

Figure 6.

Figure 6

SARS-CoV ORF3a and the immune response. Following SARS-CoV infection of ACE2 expressing cells, ORF3a is expressed in the ER induces the PERK ER stress pathway resulting in the serine phosphorylation of IFNAR and attenuation of the IFN-α JAK/STAT signalling pathway and downstream ISG induction. ORF3a has been shown to co-localise with RIP3 in lysosomes and RIP3 has been shown to promote ORF3a oligomerisation leading to the activation of TFEB and subsequent pro-IL-1β, IL-2 and IL-27 induction. ORF3a has also been shown to interact with TRAF3 triggering downstream NF-κB activation and induction of pro-IL-1β, pro-IL-18 and IL-8. ORF3a has also been shown to promote inflammasome activation, through interaction with TRAF3 and via potassium efflux, leading to cleavage of pro-IL-1β and pro-IL-18. The release of IL-8, mature IL-1β and IL-18 from SARS-CoV promotes inflammation, contributing to the immunopathology associated with SARS-CoV infection.