Herpesvirus Saimiri vFLIP provides an antiapoptotic function but is not essential for viral replication, transformation, or pathogenicity

Apoptosis of infected cells is an important host defense mechanism, and man y viruses have exploited anti-apoptotic proteins that interfere with crucia l cellular pathways. Viral FLICE inhibitory proteins (vFLIPs) are encoded b y rhadinoviruses like herpesvirus saimiri, the related Kaposi's sarcoma-ass ociated herpesvirus-human herpesvirus 8 (KSHV/HHV8), and the poxvirus respo nsible for molluscum contagiosum. The vFLIPs can block the interaction of t he death receptor-adapter complex with the cellular effector FLICE (caspase -8), and this prevents the initiation of the downstream caspase cascade. KS HV/HHV8 vFLIP overexpression can confer resistance to T-cell-mediated apopt osis and acts as a tumor progression factor in a murine B-cell lymphoma mod el. To analyze the function of herpesvirus vFLIPs in the genetic background of the virus and in a model for viral pathogenesis, we deleted the vFLIP g ene (open reading frame 71) from the genome of herpesvirus saimiri strain C 488. The viral deletion mutant was viable and replicated like the wild-type virus. An antiapoptotic effect could be attributed to the vFLIP gene, but we also show that the vFLIP gene of herpesvirus saimiri is dispensable for viral transformation of T cells in vitro and for pathogenicity in cottontop tamarins in vivo.