Figure 1. RIPK3-driven cell death during virus infections.

Multiple viruses activate RIPK3 by different upstream mechanisms during their life cycles, leading to phosphorylation of MLKL and necroptosis, as well as recruitment of FADD and caspase-8-mediated apoptosis. The survival advantage to the virus of blocking RIPK3 signaling is highlighted by the growing number of virus proteins that target activation of these pathways during species-specific co-evolution of viruses with their natural hosts. Activation or inhibition of RIPK3 signaling is often mediated by RHIM-based homotypic interactions; the RHIM in proteins containing this motif is shown as a red rectangle. (HSV, herpes simplex virus; MCMV, murine cytomegalovirus; IAV, influenza A virus; VV, vaccinia virus.)