Inhibition of apoptosis by the gamma-herpesviruses.

All members of the gamma-herpesvirus family encode genes capable of inhibiting apoptosis. Inhibition of a variety of types of apoptotic stimuli have been demonstrated for specific viral genes, including pathways induced by the immune system as well as internal pathways. Virally encoded genes inhibit the activation of caspase-8 by the TNF receptor and Fas; activate NF-kappaB to increase expression of antiapoptotic genes; inhibit interferon response; bind to p53, thereby blocking p53 dependent apoptosis; and interact with other pro- and antiapoptotic cellular genes. All gamma-herpesviruses also express viral homologues of cellular antiapoptotic genes, including one or two Bcl-2 homologues. The human gamma-herpesviruses encode genes that can inhibit apoptosis during both latent and lytic infection. During latent phase infection inhibition of apoptosis is likely important for persistence of the gamma-herpesviruses in the face of immune attack, but it is also required for maintenance of infected cells in culture. During lytic replication the virus inhibits apoptosis to prevent cell death before viral replication and spread occurs.