Inhibition of programmed cell death by cytomegaloviruses

The elimination of infected cells by programmed cell death (PCD) is one of the most ancestral defense mechanisms against infectious agents. This mechanism should be most effective against intracellular parasites, such as viruses, which depend on the host cell for their replication. However, even large and slowly replicating viruses like the cytomegaloviruses (CMVs) can prevail and persist in face of cellular suicide programs and other innate defense mechanisms. During evolution, these viruses have developed an impressive set of countermeasures against premature demise of the host cell. In the last decade, several genes encoding suppressors of apoptosis and necrosis have been identified in the genomes of human and murine CMV (HCMV and MCMV). Curiously, most of the gene products are not homologous to cellular antiapoptotic proteins, suggesting that the CMVs did not capture the genes from the host cell genome. This review summarizes our current understanding of how the CMVs suppress PCD and which signaling pathways they target.