Figure 2.

ZBP1 as a master regulator of PANoptosis during IAV infection.

ZBP1 is an innate sensor of IAV that triggers PANoptosis and inflammation. ZBP1 activation leads to its interaction with RIPK3, caspase-6, RIPK1, and caspase-8 to assemble the PANoptosome. The ZBP1-dependent PANoptosome engages NLRP3 inflammasome activation and GSDMD-dependent pyroptosis. The activation of caspase-8 leads to caspase-3, caspase-6, caspase-7 activation and apoptosis and can also cleave GSDMD, while inactivation of caspase-8 leads to phosphorylation of MLKL and necroptosis. Black lines within proteins represent the RHIM interaction domain.