Importantly, ZBP1 has been found to be a major contributor to necroptosis in both human and mouse fibroblasts following infection with both an ICP6-deficient and an ICP6 RHIM mutant HSV-1 strain (Guo et al., 2018) and our own observations suggest that this cytosolic DNA sensor functions as a mediator of cell death during HSV-1 infection in glia. Here, ZBP1 is linked to infection.