Orf3a from SARS-CoV has been shown to bind TRAF3 and activate the NLRP3 inflammasome. The activation occurs at two points. First, by ubiquinating NF-kB (p105) to stimulate its proteolytic processing into mature NF-kB (p50), which can then go on to promote the transcription of pro-IL-1B together with RELA (p65). And second, by ubiquitinating ASC (PYCARD) in the NLRP3 inflammasome, which leads to its degradtion and the activation of caspase-1 (CASP1) that goes on to catalyze the production of mature IL-1B, leading to a cytokine storm.
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