The antiviral adaptor proteins Cardif and Trif are processed and inactivated by caspases
The antiviral adaptor proteins Cardif and Trif are processed and inactivated by caspases
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DOI：
10.1038/cdd.2008.119
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发表时间：
2008-11-01
影响因子：
12.4
通讯作者：
Tschopp, J.
中科院分区：
文献类型：
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作者：
Rebsamen, M.;Meylan, E.;Tschopp, J.
病毒感染的结果取决于宿主触发强效抗病毒反应的能力和抵消它们的病毒机制之间的相互作用。虽然toll样受体(TLR)-3识别病毒衍生的双链RNA，通过TIR适配器Trif （TICAM-1）传递下游抗病毒信号，但病毒RNA传感rig样解旋酶（RLHs）使用线粒体结合的CARD蛋白Cardif （IPS-1/MAVS/VISA）。这两种抗病毒信号通路的重要性反映在以下事实中：这两种接头都是通过丙型肝炎病毒丝氨酸蛋白酶NS3-4A触发的特异性裂解而被抑制的。在这里，我们发现失活也可以通过各种促凋亡信号激活的细胞半胱天冬酶发生。在caspase依赖性切割后，这两个接子都失去了激活转录因子干扰素调节因子（IRF）和NF-kappa b的能力。重要的是，脊髓灰质炎病毒感染会触发caspase依赖性切割Cardif，这表明一些病毒激活caspase不仅是为了促进脱落和复制，而且还会损害抗病毒反应。
The outcome of a viral infection depends on the interplay between the host's capacity to trigger potent antiviral responses and viral mechanisms that counteract them. Although Toll-like receptor (TLR)-3, which recognizes virally derived double-stranded (ds) RNA, transmits downstream antiviral signaling through the TIR adaptor Trif (TICAM-1), viral RNA-sensing RIG-like helicases (RLHs) use the mitochondrial-bound CARD protein Cardif (IPS-1/MAVS/VISA). The importance of these two antiviral signaling pathways is reflected by the fact that both adaptors are inhibited through specific cleavage triggered by the hepatitis C virus serine protease NS3-4A. Here, we show that inactivation can also occur through cellular caspases activated by various pro-apoptotic signals. Upon caspase-dependent cleavage both adaptors loose their capacity to activate the transcription factors interferon regulatory factors (IRF) and NF-kappa B. Importantly, poliovirus infection triggers a caspase-dependent cleavage of Cardif, suggesting that some viruses may activate caspases not only as a mean to facilitate shedding and replication, but also to impair antiviral responses.