The membrane protein of SARS-CoV suppresses NF-κB activation
The membrane protein of SARS-CoV suppresses NF-κB activation
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DOI：
10.1002/jmv.20953
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发表时间：
2007-10-01
影响因子：
12.7
通讯作者：
Ye, Linbai
中科院分区：
文献类型：
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作者：
Fang, Xiaonan;Gao, Jinrong;Ye, Linbai
严重急性呼吸综合征冠状病毒(SARS-CoV)感染肺、肝脏、免疫器官等多个器官，引起危及生命的非典型肺炎，发病率和死亡率较高。SARS发病的分子机制仍不清楚。炎症刺激可激活I kappa B激酶(IKK)信号体，进而激活核因子kappaB(NF-kappa B)，从而影响环氧合酶-2(COX-2)和其他转录因子的基因表达。在这项工作中，我们利用免疫共沉淀试验(IPA)发现SARS-CoV膜(M)蛋白与IKKβ物理相互作用。M抑制肿瘤坏死因子-α的表达。用荧光素酶报告实验诱导核因子-kappaB的激活。进一步的研究表明，通过荧光素酶报告基因分析、RT-PCR和Western印迹分析，M蛋白抑制了COX-2的表达。M蛋白的羧基末端足以满足M蛋白的功能。综上所述，这些结果表明，SARS冠状病毒M可能通过与IKKβ直接相互作用抑制NF-kappaB的活性，导致COX-2表达降低。抑制NF-kappaB活性和COX-2表达可能参与了SARS的发病过程。
Severe acute respiratory syndrome coronavirus (SARS-CoV) infects many organs, such as lung, liver, and immune organs and causes life-threatening atypical pneumonia, SARS causes high morbidity and mortality rates. The molecular mechanism of SARS pathogenesis remains elusive. Inflammatory stimuli can activate I kappa B kinase (IKK) signalsome and subsequently the nuclear factor kappa B (NF-kappa B), which influences gene expression of cyclooxygenase-2 (Cox-2) along with other transcription factors. In this work, we found that the membrane (M) protein of SARS-CoV physically interacted with IKK beta using a co-immunoprecipitation assay (IPA). Expression of M suppressed tumor necrosis factor alpha (TNF-alpha.) induced NF-kappa B activation using a luciferase reporter assay. Further investigation showed M protein suppressed Cox-2 expression using a luciferase reporter gene assay, RT-PCR and Western blot analysis. The carboxyl terminal of M protein was sufficient for the M protein function. Together, these results indicate that SARS-CoV M suppresses NF-kappa B activity probably through a direct interaction with IKK beta, resulting in lower Cox-2 expression. Suppression of NF-kappa B activity and Cox-2 expression may contribute to SARS pathogenesis.