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.