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. 2021 Jun 17;22(3):141–160. doi: 10.1038/s41435-021-00140-w

Fig. 4. Simplified schematic diagram of a conceptual model illustrating release of DAMPs from SARS-CoV/viroporin-induced pyroptotic cells.

Fig. 4

The first priming step is exemplified by IFN receptor-triggered transcriptional pathways (NF-κB activation) to promote upregulation of NLRP3 and pro-IL-1β/pro-IL18 expression. The activation step is proposed to be triggered by SARS CoV viroporins via recruitment of NLRP3 to dTGN in the form of an early and common cellular event caused, for example, by virus-induced ER stress, ER stress-induced mitochondrial ROS production, calcium mobilization, and enhanced potassium efflux and (marked by purple arrows). Activated Gasdermin D-N then binds to lipids in the plasma membrane and forms large pores, leading to pyroptotic cell death and release of cellular contents such as DAMPs and matured IL-1β and IL-18. ASC apoptosis-associated speck-like protein containing a caspase recruitment domain, C C-terminal domain, CARD caspase-activating and recruiting domain, dTGN dispersed trans-Golgi network, eATP extracellular adenosine triphosphate, K+ potassium, NF-κB nuclear factor kappa B, IL interleukin, LRR leucine-rich repeats, N N-terminal domain, NACHT (domain), neuronal apoptosis inhibitor protein (NAIP), MHC-Class II transactivator/ transcription activator (CIITA), plant het product (HET-E), and telomerase-associated protein 1 (TP1) protein, NLRP3 nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3, PI, phosphatidylinositol-4-phosphate, PYD pyrin domain, P2X7R P2X purinoceptor, ROS reactive oxygen species, TLR4 Toll-like receptor 4. Note: This figure is modified from Fig. 2.1 (including the legend with Refs. and based on findings of Chen and Chen [70]) published in Ref. [11] (Section 2.2.5.3, p. 20). Further Sources: [61–69].