GSDME deficiency in mice alleviated pathological symptoms of enterovirus 71 infection, demonstrating that GSDME is required for EV71-induced pyroptosis and severe disease.
GSDME is essential for EV71-induced pyroptosis and pathogenesis, highlighting its role in the severity of enterovirus 71 infection.
Pyroptosis is an inflammatory form of programmed cell death that is executed by the gasdermin (GSDM)-N domain of GSDM family proteins, which form pores in the plasma membrane. Although pyroptosis acts as a host defense against invasive pathogen infection, its role in the pathogenesis of enterovirus 71 (EV71) infection is unclear. In the current study, we found that EV71 infection induces cleavage of GSDM E (GSDME) by using western blotting analysis, an essential step in the switch from caspase-3-mediated apoptosis to pyroptosis. We show that this cleavage is independent of the 3C and 2A proteases of EV71. However, caspase-3 activation is essential for this cleavage, as GSDME could not be cleaved in caspase-3-KO cells upon EV71 infection. Further analyses showed that EV71 infection induced pyroptosis in WT cells but not in caspase-3/GSDME double-KO cells. Importantly, GSDME is required to induce severe disease during EV71 infection, as GSDME deficiency in mice was shown to alleviate pathological symptoms. In conclusion, our results reveal that GSDME is important for the pathogenesis of EV71 via mediating initiation of pyroptosis.
Dong et al. (Wed,) conducted a other in Enterovirus 71 (EV71) infection. GSDME deficiency vs. Wild-type (WT) was evaluated on Induction of pyroptosis and severe disease symptoms. GSDME deficiency in mice alleviated pathological symptoms of enterovirus 71 infection, demonstrating that GSDME is required for EV71-induced pyroptosis and severe disease.