Recent studies demonstrate that the GSDME-N can permeabilize the mitochondrial membrane and activate the intrinsic apoptotic pathway (Rogers et al., 2019), which implies the possibility that during ZIKV infection, the caspase-8-mediated activation of GSDME consequently induces the caspase-9-associated intrinsic apoptosis by targeting mitochondrial, thereby creating a self-amplifying feed-forward loop through consecutively activating caspase-3. This evidence concerns the gene CASP3 and Zika virus infectious disease.