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. Author manuscript; available in PMC: 2016 Nov 18.
Published in final edited form as: Virology. 2015 Mar 24;479-480:160–166. doi: 10.1016/j.virol.2015.03.016

Figure 1. Evolutionary relationships in cell autonomous death pathways and virus-encoded countermeasures.

Figure 1

Programmed cell death (PCD) pathways include the mitochondrial (or cell-intrinsic) death pathway that eliminates cells during development and homeostatic turnover as well as in host defense [9,10,53,100]. Viral (v)Bcl2 homologs and other virus-encoded mitochondrial suppressors block mitochondrial PCD, establishing conditions that selected for a Casp8-like activity to directly trigger effector caspases, bypassing mitochondrial Bcl2 function. Viruses adaptation included Casp8-targeted cell death suppressors, some specific, like herpesvirus vFLIPs, betaherpesvirus vICA, and some nonspecific, like the poxvirus serpin, CrmA. RIP3-dependent necroptosis via RHIM-dependent interaction with RIP1, TRIF or DAI, enables the host to bypass the impact of virus-encoded Casp8 inhibitors. The examples of MCMV vIRA and HSV1/HSV2 R1 RHIM signaling competitors are the first examples of viral suppressors of necroptosis [2,3,5,20]. Note that HSV1 ICP6 inhibits necroptosis in human cells but promotes necroptosis in mouse cells [98,99]. This depiction is adapted from [9].