Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-kappaB.
Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-kappaB.
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DOI：
10.1016/j.virol.2007.04.009
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发表时间：
2007-09-01
期刊：
影响因子：
3.7
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Zhang X;Wu K;Wang D;Yue X;Song D;Zhu Y;Wu J
SARS患者急性期血清IL-6水平升高，并伴有肺部病变。为了评估这一事件背后的机制，我们研究了SARS-CoV蛋白在调节IL-6中的作用。结果表明，病毒核衣壳（N）蛋白以浓度依赖性方式激活IL-6的表达。启动子分析提示NF-κB结合元件是N蛋白调控IL-6表达所必需的。进一步的研究表明，N蛋白与启动子上的NF-κB元件直接结合。我们还发现，N蛋白通过促进NF-κB从胞浆到细胞核的移位，通过NF-κB激活IL-6的表达。突变分析表明，N蛋白的两个区域是其激活IL-6的功能所必需的。这些结果为理解SARS冠状病毒N蛋白的功能和致病机制提供了新的见解。
High levels of interleukin-6 (IL-6) in the acute stage associated with lung lesions were found in SARS patients. To evaluate the mechanisms behind this event, we investigated the roles of SARS-CoV proteins in the regulation of IL-6. Results showed that the viral nucleocapsid (N) protein activated IL-6 expression in a concentration-dependent manner. Promoter analyses suggested that NF-κB binding element was required for IL-6 expression regulated by N protein. Further studies demonstrated that N protein bound directly to NF-κB element on the promoter. We also showed that N protein activated IL-6 expression through NF-κB by facilitating the translocation of NF-κB from cytosol to nucleus. Mutational analyses revealed that two regions of N protein were essential for its function in the activation of IL-6. These results provided new insights into understanding the mechanism involved in the function of SARS-CoV N protein and pathogenesis of the virus.
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