A working model of SARS-CoV-induced inflammasome activation. SARS-CoV can activate both signal 1 (priming) and signal 2 (activation). Upregulation of pro-IL-1β transcription is achieved by NF-κB activation. Two mechanisms of IL-1β maturation have been proposed. In the first model, potassium ion efflux is promoted by ORF3a and E proteins, leading to NLRP3 inflammasome assembly. Alternatively, ORF3a promotes ASC ubiquitination and consequent assembly of inflammasome. ORG8b interacts with and activates NLRP3. Activation of inflammasome leads to proteolytic cleavage of pro-caspase 1 and pro-IL-1β. ASC, apoptosis-associated speck-like protein containing a CARD. CASP1, caspase 1. IKK, IκB kinase. IL-1, interleukin-1. LPS, lipopolysaccharides. NLRP3, NACHT, LRR, and PYD domains-containing protein 3. NEMO, NF-κB essential modulator. TNF-α, tumour necrosis factor α.