Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors

Viruses have evolved many distinct strategies to avoid the host's apoptotic response1,2. Here we describe a new family of viral inhibitors (v-FLIPs) which interfere with apoptosis signalled through death receptors3 and which are present in several γ-herpesviruses (including Kaposi's-sarcoma-associated human herpesvirus-8), as well as in the tumorigenic human molluscipoxvirus4. v-FLIPs contain two death-effector domains which interact with the adaptor protein FADD5,6, and this inhibits the recruitment and activation of the protease FLICE7,8 by the CD95 death receptor3. Cells expressing v-FLIPs are protected against apoptosis induced by CD95 or by the related death receptors TRAMP9–12 and TRAIL-R. The herpesvirus saimiri FLIP is detected late during the lytic viral replication cycle, at a time when host cells are partially protected from CD95-ligand-mediated apoptosis. Protection of virus-infected cells against death-receptor-induced apoptosis may lead to higher virus production and contribute to the persistence and oncogenicity13 of several FLIP-encoding viruses.