Thome M, Schneider P, Hofmann K, Fickenscher H, Meinl E, Neipel F, Mattmann C, Burns K, Bodmer J L, Schröter M, Scaffidi C, Krammer P H, Peter M E, Tschopp J
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Nature. 1997 Apr 3;386(6624):517-21. doi: 10.1038/386517a0.
Viruses have evolved many distinct strategies to avoid the host's apoptotic response. Here we describe a new family of viral inhibitors (v-FLIPs) which interfere with apoptosis signalled through death receptors and which are present in several gamma-herpesviruses (including Kaposi's-sarcoma-associated human herpesvirus-8), as well as in the tumorigenic human molluscipoxvirus. v-FLIPs contain two death-effector domains which interact with the adaptor protein FADD, and this inhibits the recruitment and activation of the protease FLICE by the CD95 death receptor. Cells expressing v-FLIPs are protected against apoptosis induced by CD95 or by the related death receptors TRAMP 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 oncogenicity of several FLIP-encoding viruses.
病毒已经进化出许多独特的策略来逃避宿主的凋亡反应。在此，我们描述了一个新的病毒抑制剂家族（v-FLIPs），它们干扰通过死亡受体发出信号的凋亡过程，存在于几种γ-疱疹病毒（包括与卡波西肉瘤相关的人类疱疹病毒8型）以及致瘤性人类痘病毒中。v-FLIPs包含两个死亡效应结构域，它们与衔接蛋白FADD相互作用，这抑制了CD95死亡受体对蛋白酶FLICE的募集和激活。表达v-FLIPs的细胞可免受CD95或相关死亡受体TRAMP和TRAIL-R诱导的凋亡。在溶细胞病毒复制周期后期可检测到赛米利疱疹病毒FLIP（herpesvirus saimiri FLIP），此时宿主细胞受到部分保护，免受CD95配体介导的凋亡。保护病毒感染的细胞免受死亡受体诱导的凋亡可能导致更高的病毒产量，并有助于几种编码FLIP的病毒的持续存在和致癌性。
