Extraordinary GU-rich single-strand RNA identified from SARS coronavirus contributes an excessive innate immune response.
Extraordinary GU-rich single-strand RNA identified from SARS coronavirus contributes an excessive innate immune response.
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从 SARS 冠状病毒中鉴定出的富含 GU 的非凡单链 RNA 有助于过度的先天免疫反应
DOI：
10.1016/j.micinf.2012.10.008
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发表时间：
2013-03
影响因子：
5.8
通讯作者：
Zhou H
中科院分区：
文献类型：
--
作者：
Li Y;Chen M;Cao H;Zhu Y;Zheng J;Zhou H
SARS是一场危险的细胞因子风暴，涉及免疫紊乱，但其发病机制的许多方面仍不清楚。为了深入揭示宿主与SARS冠状病毒的相互作用，基于病原体相关分子模式的基本结构特征，我们建立了一种新的寻找潜在致病分子的生物信息学方法，并鉴定了一组高密度分布于基因组中的SARS冠状病毒特异性富含GU的ssRNA片段。体外实验结果表明，代表性的SARS-CoV ssRNA具有较强的免疫刺激活性，可通过TLR 7和TLR 8诱导相当水平的促炎细胞因子TNF-α、IL-6和IL-12的释放，比以前从其他病毒中发现的强刺激性ssRNA 40高近2倍。此外，SARS-CoV ssRNA在体内实验中能够引起小鼠的急性肺损伤，具有较高的死亡率。这表明SARS-CoV特异性富含GU的ssRNA在与先天免疫失调相关的细胞因子风暴中起着非常重要的作用。本研究不仅为SARS冠状病毒感染过程中过度炎症反应导致的免疫病理损伤提供了新的证据，而且为新的治疗策略提供了有用的线索。
A dangerous cytokine storm occurs in the SARS involving in immune disorder, but many aspects of the pathogenetic mechanism remain obscure since its outbreak. To deeply reveal the interaction of host and SARS-CoV, based on the basic structural feature of pathogen-associated molecular pattern, we created a new bioinformatics method for searching potential pathogenic molecules and identified a set of SARS-CoV specific GU-rich ssRNA fragments with a high-density distribution in the genome. In vitro experiments, the result showed the representative SARS-CoV ssRNAs had powerful immunostimulatory activities to induce considerable level of pro-inflammatory cytokine TNF-a, IL-6 and IL-12 release via the TLR7 and TLR8, almost 2-fold higher than the strong stimulatory ssRNA40 that was found previously from other virus. Moreover, SARS-CoV ssRNA was able to cause acute lung injury in mice with a high mortality rate in vivo experiment. It suggests that SARS-CoV specific GU-rich ssRNA plays a very important role in the cytokine storm associated with a dysregulation of the innate immunity. This study not only presents new evidence about the immunopathologic damage caused by overactive inflammation during the SARS-CoV infection, but also provides a useful clue for a new therapeutic strategy.
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影响因子：
5
作者：
Cameron MJ;Bermejo-Martin JF;Danesh A;Muller MP;Kelvin DJ
通讯作者：
Kelvin DJ
影响因子：
7.3
作者：
He, L.;Ding, Y.;Jiang, S.
通讯作者：
Jiang, S.
影响因子：
15.8
作者：
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DOI：
10.1016/j.bbrc.2004.09.106
发表时间：
2004-11-12
影响因子：
3.1
作者：
He Y;Zhou Y;Liu S;Kou Z;Li W;Farzan M;Jiang S
通讯作者：
Jiang S
影响因子：
5
作者：
Frieman, Matthew;Heise, Mark;Baric, Ralph
通讯作者：
Baric, Ralph