Negative Regulation of RIG-I-Mediated Innate Antiviral Signaling by SEC14L1
Negative Regulation of RIG-I-Mediated Innate Antiviral Signaling by SEC14L1
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DOI：
10.1128/jvi.01073-13
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发表时间：
2013-09-01
影响因子：
5.4
通讯作者：
Chen, Dan-Ying
中科院分区：
文献类型：
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作者：
Li, Meng-Tong;Di, Wei;Chen, Dan-Ying
视黄酸诱导基因I （RIG-I）是识别来自RNA病毒的核酸并触发干扰素（ifn - β）产生的关键传感器。由于rig - 1在抗病毒先天免疫中的重要作用，其活性必须受到严格控制。在这里，我们使用酵母双杂交筛选来鉴定SEC14家族成员SEC14L1作为rig - i相关的负调控因子。转染的SEC14L1与RIG-I相互作用，内源性SEC14L1以病毒感染诱导的方式与RIG-I相关。过表达SEC14L1抑制RIG-I诱导的ifn - β启动子的转录活性，但不抑制tank结合激酶1 （TBK1）和干扰素调节因子3 （IRF3）。HEK293T细胞和HT1080细胞中内源性SEC14L1的敲低可增强rig - 1和仙台病毒引发的ifn - β的产生，并减弱新城疫病毒的复制。SEC14L1与RIG-I的n端结构域（RIG-I caspase activation and recruitment domain [RIG-I- card]）相互作用，并与VISA/MAVS/IPS-1/Cardif竞争RIG-I- card结合。结构域定位进一步表明，SEC14L1的相互作用和抑制功能需要PRELI-MSF1和CRAL-TRIO结构域，而不需要GOLD结构域。这些发现提示SEC14L1
Retinoic acid-inducible gene I (RIG-I) is a key sensor for recognizing nucleic acids derived from RNA viruses and triggers beta interferon (IFN-beta) production. Because of its important role in antiviral innate immunity, the activity of RIG-I must be tightly controlled. Here, we used yeast two-hybrid screening to identify a SEC14 family member, SEC14L1, as a RIG-I-associated negative regulator. Transfected SEC14L1 interacted with RIG-I, and endogenous SEC14L1 associated with RIG-I in a viral infection-inducible manner. Overexpression of SEC14L1 inhibited transcriptional activity of the IFN-beta promoter induced by RIG-I but not TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3). Knockdown of endogenous SEC14L1 in both HEK293T cells and HT1080 cells potentiated RIG-I and Sendai virus-triggered IFN-beta production as well as attenuated the replication of Newcastle disease virus. SEC14L1 interacted with the N-terminal domain of RIG-I (RIG-I caspase activation and recruitment domain [RIG-I-CARD]) and competed with VISA/MAVS/IPS-1/Cardif for RIG-I-CARD binding. Domain mapping further indicated that the PRELI-MSF1 and CRAL-TRIO domains but not the GOLD domain of SEC14L1 are required for interaction and inhibitory function. These findings suggest that SEC14L1