BinCARD2 as a positive regulator of interferon response in innate immunity
BinCARD2 as a positive regulator of interferon response in innate immunity
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DOI：
10.1016/j.bbrc.2019.02.029
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发表时间：
2019-04-02
影响因子：
3.1
通讯作者：
Takaoka, Akinori
中科院分区：
文献类型：
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作者：
Suzuki, Hiraku;Kameyama, Takeshi;Takaoka, Akinori
天然免疫是一种主要识别和排除病原微生物的系统。MAVS/IPS-1/Cardif/Visa作为RIG-I样受体（RLR）的衔接蛋白发挥作用，并在RNA病毒的抗病毒蛋白、干扰素（IFN）的产生中起关键作用。然而，激活机制尚未完全了解。在这里，我们表明BinCARD同种型2（BinCARD 2），携带CARD结构域结构像MAVS，在先天免疫反应中发挥作用。BinCARD 2的敲低降低了RLR配体诱导的IFN-β mRNA表达和IFNB启动子的激活。通过过表达MAVS或TBK 1激活IFNB启动子被BinCARD 2沉默抑制，但通过过表达TRIF或组成型激活的IRF-3对IFNB启动子激活没有影响。此外，我们通过免疫沉淀证实BinCARD 2蛋白与MAVS相关，而不是TBK 1，并与MAVS共定位。因此，我们研究了BinCARD 2是否参与MAVS活化，并显示siBinCARD 2不影响RIG-I/MAVS结合，但损害MAVS寡聚化。此外，我们用水泡性口炎病毒（VSV）感染A549细胞，发现BinCARD 2敲低降低了VSV感染后IFN-β和IL-6 mRNA的诱导。因此，这些数据可能表明BinCARD 2与MAVS结合以正向调节RIG-I样受体途径中的寡聚化并激活先天性免疫应答。(C)2019爱思唯尔公司All rights reserved.
Innate immunity is a system that recognizes primarily and excludes pathogenic microorganism. MAVS/IPS-1/Cardif/Visa functions as an adapter protein for RIG-I like receptors (RLRs) and plays a key role in the production of antiviral proteins, interferons (IFNs), for RNA viruses. However, the activation mechanism is not fully understood. Here, we show that BinCARD isoform2 (BinCARD2), carrying CARD domain structure like MAVS, functions in innate immune response. Knockdown of BinCARD2 reduced the RLR ligand-induced expression of IFN-beta mRNA and activation of the IFNB promoter. The activation of the IFNB promoter by overexpression of MAVS or TBK1 was suppressed by silencing of BinCARD2, but no effect on IFNB promoter activation by overexpression of TRIF or constitutive activated IRF-3. Furthermore, we confirmed that BinCARD2 protein associated with MAVS but not TBK1 by immunoprecipitation and colocalized with MAVS. Accordingly, we investigated whether BinCARD2 was involved in MAVS activation and showed that siBinCARD2 did not affect RIG-I/MAVS binding but impaired the MAVS oligomerization. Moreover, we infected A549 cells with vesicular stomatitis virus (VSV) and found that induction of IFN-beta and IL-6 mRNA after VSV infection was decreased by BinCARD2 knockdown. Thus, these data may suggest that BinCARD2 associates with MAVS to positively modulate the oligomerization in the RIG-I like receptors pathway and activates innate immune response. (C) 2019 Elsevier Inc. All rights reserved.