from A. Louise McCormick and Edward S. Mocarski writing in Cytomegaloviruses: From Molecular Pathogenesis to Intervention:
Cytomegalovirus (CMV) deploys multiple strategies to overcome host intrinsic, innate, and adaptive responses that limit infection by triggering cell death. Multiple cell death suppressors are encoded by cytomegaloviruses infecting humans, monkeys and rodents. The viral inhibitor of caspase activation (vICA) and even the viral mitochondrial-localized inhibitor of apoptosis (vMIA) represent evolutionarily conserved strategies, whereas viral inhibitor of receptor-interacting protein kinase (RIP) activation (vIRA), the mitochondrial complex I-associated b2.7 RNA and other viral gene products whose mechanisms are not fully understood, appear to have evolved independently in primate and rodent CMVs. Initiators, effectors and interactions between CMV-induced cell death pathways have begun to emerge, through studies in cell culture and intact animals. It has become very clear that many cell death pathways are targeted by CMV-encoded cell death suppressors. Indeed, this subfamily of viruses has provided fundamental insights into pathogen-triggered regulated cell death pathways in mammals. Whereas both intrinsic and extrinsic caspase-dependent apoptosis was well-established, studies in CMV brought serine protease-dependent programmed cell death and RIP3 programmed necrotic death pathways to the fore. Virus-encoded cell death suppressors contribute resistance to cell stress as well as resistance to disruption of critical metabolic and respiratory activities. Challenges for investigators interested in this area continue to be integration of findings using diverse viral strains that impact metabolic and stress pathways with seemingly subtle differences.
Further reading: Cytomegaloviruses: From Molecular Pathogenesis to Intervention