Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors
Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors
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DOI：
10.1038/386517a0
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发表时间：
1997-04
期刊：
影响因子：
64.8
通讯作者：
M. Thome;P. Schneider;K. Hofmann;H. Fickenscher;E. Meinl;F. Neipel;C. Mattmann;K. Burns;J. Bodm
中科院分区：
文献类型：
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作者：
M. Thome;P. Schneider;K. Hofmann;H. Fickenscher;E. Meinl;F. Neipel;C. Mattmann;K. Burns;J. Bodm
病毒已经进化出许多不同的策略来避免宿主的凋亡反应1，2。在这里，我们描述了一个新的病毒抑制剂家族（v-FLIP），它通过死亡受体3干扰细胞凋亡信号，存在于几种γ-疱疹病毒（包括卡波西肉瘤相关的人类疱疹病毒-8），以及致瘤性人类软体动物痘病毒4。v-FLIP包含两个死亡效应域，其与衔接蛋白FADD相互作用5，6，这抑制了CD 95死亡受体3对蛋白酶FLICE 7，8的募集和激活。表达v-FLIPs的细胞被保护免于由CD 95或相关死亡受体TRAMP 9 - 12和TRAIL-R诱导的凋亡。疱疹病毒松鼠猴FLIP在裂解病毒复制周期的后期被检测到，此时宿主细胞被部分保护免于CD 95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细胞凋亡可能导致更高的病毒产量，并有助于几种FLIP编码病毒的持久性和致癌性13。
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 receptors3and 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 FLICE7,8by the CD95 death receptor3. Cells expressing v-FLIPs are protected against apoptosis induced by CD95 or by the related death receptors TRAMP9–12and 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 oncogenicity13of several FLIP-encoding viruses.