An "Old" protein with a new story: Coronavirus endoribonuclease is important for evading host antiviral defenses.

An "Old" protein with a new story: Coronavirus endoribonuclease is important for evading host antiviral defenses.
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一种具有新故事的“旧”蛋白质:冠状病毒内切核糖核酸酶对于逃避宿主抗病毒防御非常重要。

DOI:
10.1016/j.virol.2017.12.024
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发表时间:
2018-04
期刊:
影响因子:
3.7
通讯作者:
Baker SC
Baker SC
中科院分区:
医学3区
文献类型:
--
作者:
Deng X;Baker SC

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在这里,我们回顾一下冠状病毒内切核糖核酸酶 (EndoU) 的演变故事。冠状病毒 EndoU 在非结构蛋白 (nsp) 15 序列内编码,该序列最初被鉴定为病毒复制复合物的组成部分。生化和结构研究揭示了 nsp15/EndoU 的酶性质,这被认为对于 Nidovirales 目病毒的独特复制周期至关重要。然而,nsp15 在冠状病毒复制中的作用是神秘的,因为 EndoU 缺陷的冠状病毒是可行的,并且在成纤维细胞中复制到接近野生型病毒的水平。最近的研究揭示了我们对 EndoU 作用的理解取得了突破,表明 EndoU 介导巨噬细胞中宿主传感器逃避病毒双链 RNA 识别。 nsp15/EndoU 功能的这一新发现为研究病毒 EndoU 如何促进发病机制以及利用这种酶用于针对致病性冠状病毒的治疗和疫苗设计提供了新的机会。
Here we review the evolving story of the coronavirus endoribonuclease (EndoU). Coronavirus EndoU is encoded within the sequence of nonstructural protein (nsp) 15, which was initially identified as a component of the viral replication complex. Biochemical and structural studies revealed the enzymatic nature of nsp15/EndoU, which was postulated to be essential for the unique replication cycle of viruses in the order Nidovirales. However, the role of nsp15 in coronavirus replication was enigmatic as EndoU-deficient coronaviruses were viable and replicated to near wild-type virus levels in fibroblast cells. A breakthrough in our understanding of the role of EndoU was revealed in recent studies, which showed that EndoU mediates the evasion of viral double-stranded RNA recognition by host sensors in macrophages. This new discovery of nsp15/EndoU function leads to new opportunities for investigating how a viral EndoU contributes to pathogenesis and exploiting this enzyme for therapeutics and vaccine design against pathogenic coronaviruses.
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