小柯机器人

中国科学家解析沙粒病毒复制机器结构
2020-03-19 15:33

近日,中国科学院微生物研究所施一和高福等研究人员合作解析了沙粒病毒复制机器的结构。相关论文于2020年3月18日在线发表在《自然》杂志上。

研究人员报道了Lassa和Machupo病毒聚合酶处于与apo和启动子结合状态下的近原子分辨率结构。这些结构显示出与流感病毒和本雅病毒聚合酶相似的总体结构,但具有独特的局部特征,包括调节聚合酶活性的沙粒病毒特异性插入结构域。值得注意的是,在不需要通过5'-病毒RNA进行变构激活(对于流感病毒和布尼亚病毒聚合酶都是必需的)的情况下,砂粒病毒聚合酶的有序活性位点能够固有地开启。而且,二聚化可以促进聚合酶活性。这些发现提高了人们对砂粒病毒复制机制的理解,并为开发抗病毒疗法提供了重要基础。
 
据介绍,沙粒病毒可引起人类和其他动物的严重出血热和神经系统疾病,例如Lassa哺乳动物沙粒病毒、Machupo哺乳动物沙粒病毒和淋巴细胞性脉络丛脑膜炎病毒,这对公共卫生构成了极大的威胁。这些病毒编码一个大型多域RNA依赖的RNA聚合酶,用于病毒基因组的转录和复制。病毒聚合酶是主要的抗病毒治疗靶标之一。但是,目前尚不知道沙粒病毒聚合酶的结构。
 
附:英文原文

Title: Structural insight into arenavirus replication machinery

Author: Ruchao Peng, Xin Xu, Jiamei Jing, Min Wang, Qi Peng, Sheng Liu, Ying Wu, Xichen Bao, Peiyi Wang, Jianxun Qi, George F. Gao, Yi Shi

Issue&Volume: 2020-03-18

Abstract: Arenaviruses can cause severe haemorrhagic fever and neurological diseases in humans and other animals, exemplified by Lassa mammarenavirus, Machupo mammarenavirus and lymphocytic choriomeningitis virus, posing great threats to public health1,2,3,4. These viruses encode a large multi-domain RNA-dependent RNA polymerase for transcription and replication of the viral genome5. Viral polymerases are one of the leading antiviral therapeutic targets. However, the structure of arenavirus polymerase is not yet known. Here we report the near-atomic resolution structures of Lassa and Machupo virus polymerases in both apo and promoter-bound forms. These structures display a similar overall architecture to influenza virus and bunyavirus polymerases but possess unique local features, including an arenavirus-specific insertion domain that regulates the polymerase activity. Notably, the ordered active site of arenavirus polymerase is inherently switched on, without the requirement for allosteric activation by 5′-viral RNA, which is a necessity for both influenza virus and bunyavirus polymerases6,7. Moreover, dimerization could facilitate the polymerase activity. These findings advance our understanding of the mechanism of arenavirus replication and provide an important basis for developing antiviral therapeutics.

DOI: 10.1038/s41586-020-2114-2

Source: https://www.nature.com/articles/s41586-020-2114-2

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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