The Open Reading Frame 7b of the SARS‐CoV‐2 Disperse Trans‐Golgi and Activate the NLRP3 Inflammasome

Inflammasomes orchestrate the inflammatory response against bacterial and viral infections, thereby initiating the synthesis of pro-inflammatory cytokines, mainly IL-1β and IL-18. SARS-CoV-2 infection induces an inflammatory response mediated by the activation of NLRP1 and NLRP3 inflammasomes. In this study, we demonstrated that the open reading frame 7b (ORF7b) accessory protein of SARS-CoV-2 induces the NLRP3 inflammasome in a recombinant HEK293T model. This resulted in an increase in the distribution of NLRP3 puncta, ASC-specking cells, and caspase-1 activation. ORF7b expression also induced the dispersion of the trans-Golgi network, a well-known step in the activation of the NLRP3 inflammasome. This study proposes a novel additional mechanism by which SARS-CoV-2 promotes NLRP3 inflammasome activation by ORF7b.