Figure 6.

DNA viruses suppress apoptotic processes. Viruses exploit host extrinsic and intrinsic apoptotic pathways via distinct viral proteins (red). Initiation of the extrinsic pathway is inhibited by virus-encoded TNF receptor suppressors. Downstream of the Fas/TNF receptors, within the cytosol, the activation of caspase-8 is inhibited by vFLIPS. The inhibition of caspase-8 will shut off the caspase cascade. In addition, viruses target other caspases by caspase suppressors. To prevent the activation of the intrinsic pathway, viral proteins mimic host Bcl-2 proteins and regulate mitochondrial membrane potential by recruiting these proteins to the outer membrane of mitochondria. This recruitment will reduce the release of APAF1, cytochrome c, and other mitochondria apoptotic factors. Therefore, these viral Bcl-2 homologues can suppress the activation of caspase-9, and in turn, apoptosis. P53 is critically involved in the regulation of the expression of pro-apoptotic factors, thus it constitutes a target of some viruses. A number of viral proteins function as p53 suppressors that modulate the levels of pro-apoptotic and anti-apoptotic genes. Of note, oxidative stress can be controlled by viral products, such as MCV MC066L, and baculovirus p35 and IAP. These viral proteins prevent host cells from ROS mediated apoptosis, but the underlying mechanisms await further characterization.