It was found that caspase-8 inhibitor remarkably inhibited the cell membrane rupture, LDH release, and GSDME cleavage in infected cells, while inhibition of caspase-9 only slightly inhibited ZIKV-induced activation of GSDME and did not significantly affect ZIKV-induced lytic cell death (Figure 3D-F, and Figure 3—figure supplement 1D), suggesting caspase-8 rather than caspase-9 may play a major role in the activation of caspase-3 and GSDME during ZIKV infection in JEG-3 cells. Here, CASP8 is linked to Zika virus infectious disease.