Activation of NF-κB by the full-length nucleocapsid protein of the SARS coronavirus

Activation of NF-κB by the full-length nucleocapsid protein of the SARS coronavirus
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DOI:
10.1111/j.1745-7270.2005.00082.x
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发表时间:
2005-09-01
影响因子:
3.7
通讯作者:
Wu, ZH
Wu, ZH
中科院分区:
生物学3区
文献类型:
--
作者:
Liao, QJ;Ye, LB;Wu, ZH

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严重急性呼吸综合征冠状病毒(SARS-CoV)是2003年全球范围内爆发的SARS的主要病原体。SARS-CoV引起非典型肺炎的机制尚不清楚。核因子 kappa B (NF-kappa B) 是一种关键转录因子,可激活众多参与细胞免疫反应和炎症的基因。许多研究表明NF kappa B在肺部疾病的发病机制中发挥着重要作用。在本研究中,我们通过荧光素酶活性测定研究了 SARS-CoV 核衣壳 (N) 蛋白和 NF-κ B 之间可能的调控相互作用。我们的结果表明,SARS-CoV N 蛋白仅在易受 SARS-CoV 感染的 Vero E6 细胞中显着激活 NF-kappa B,但在 Vero 或 HeLa 细胞中则不然。这表明 NF-κ B 激活是细胞特异性的。此外,表达 N 蛋白的 Vero E6 细胞中 NF-κ B 的激活具有剂量依赖性。进一步的实验表明,N蛋白中有不止一个功能域负责NF-κB的激活。我们的数据表明 N 蛋白在 SARS 发病机制中可能发挥作用。
The severe acute respiratory syndrome coronavirus (SARS-CoV) is the major causative agent for the worldwide outbreak of SARS in 2003. The mechanism by which SARS-CoV causes atypical pneumonia remains unclear. The nuclear factor kappa B (NF-kappa B) is a key transcription factor that activates numerous genes involved in cellular immune response and inflammation. Many studies have shown that NF kappa B plays an important role in the pathogenesis of lung diseases. In this study, we investigated the possible regulatory interaction between the SARS-CoV nucleocapsid (N) protein and NF-kappa B by luciferase activity assay. Our results showed that the SARS-CoV N protein can significantly activate NF-kappa B only in Vero E6 cells, which are susceptible to SARS-CoV infection, but not in Vero or HeLa cells. This suggests that NF-kappa B activation is cell-specific. Furthermore, NF-kappa B activation in Vero E6 cells expressing the N protein is dose-dependent. Further experiments showed that there is more than one function domain in the N protein responsible for NF-kappa B activation. Our data indicated the possible role of the N protein in the pathogenesis of SARS.