2019新型冠状病毒基因组特征和流行病学
2020-02-11   阅读:1554   来源:柳叶刀

中国疾病预防控制中心谭文杰联合山东医学科学院山东第一医科大学史卫峰课题组在研究中取得进展。他们详细分析了2019新型冠状病毒的基因组特征和流行病学。这一研究成果于2020年1月30日发表在国际顶尖学术期刊《柳叶刀》上。

2019年12月下旬,中国武汉报告了因不明微生物制剂引起的病毒性肺炎患者。随后一种新型冠状病毒被鉴定为致病病原体,暂定名为2019新型冠状病毒(2019-nCoV)。截至2020年1月26日,已确认2019-nCoV感染2000余例,其中大部分为居住在武汉或来武汉旅游的人群,并已确认可人传人。

研究组对9名住院患者的支气管肺泡灌洗液样本和培养的分离物进行了下一代测序,其中8名患者曾去过武汉华南海鲜市场。从这些人中获得了2019-nCoV完整和部分的基因组序列。对这些2019-nCoV基因组和其他冠状病毒基因组进行系统发育分析,以确定病毒的进化史,并帮助推断其可能的起源。通过同源性模型研究病毒可能的受体结合特性。

9例患者2019-nCoV的10个基因组序列极为相似,序列同源性达99.98%以上。值得注意的是,2019-nCoV与2018年在中国东部舟山采集的两种来源蝙蝠的严重急性呼吸综合征(SARS)样冠状病毒bat-SL-CoVZC45和bat-SL-CoVZXC21密切相关(88%的同源性),但与SARS冠状病毒(约79%)和MERS冠状病毒(约50%)的距离较远。

系统发育分析表明,2019-nCoV属于β-冠状病毒属的Sarbecovirus亚属,与最近的亲缘种bat-SL-CoVZC45和bat-SL-covzcx21相比,分枝长度相对较长,在遗传上与SARS-CoV不同。值得注意的是,同源性模型显示2019-nCoV与SARS-CoV具有相似的受体结合区结构,尽管在一些关键残基上存在氨基酸变异。

2019-nCoV与SARS-CoV有较大差异,可认为是一种新型人感染β-冠状病毒。虽然系统发育分析表明蝙蝠可能是该病毒的原始宿主,但在武汉海鲜市场出售的动物可能是一种中间宿主,有助于病毒传入人类。重要的是,结构分析表明2019-nCoV可能会与人类血管紧张素转换酶2受体结合。这种病毒未来的进化、适应和传播需紧急调查。

附:英文原文

Title: Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

Author: Roujian Lu, Xiang Zhao, Juan Li, Peihua Niu, Bo Yang, Honglong Wu, Wenling Wang, Hao Song, Baoying Huang, Na Zhu, Yuhai Bi, Xuejun Ma, Faxian Zhan, Liang Wang, Tao Hu, Hong Zhou, Zhenhong Hu, Weimin Zhou, Li Zhao, Jing Chen, Yao Meng, Ji Wang, Yang Lin, Jianying Yuan, Zhihao Xie, Jinmin Ma, William J Liu, Dayan Wang, Wenbo Xu, Edward C Holmes, George F Gao, Guizhen Wu, Weijun Chen, Weifeng Shi, Wenjie Tan

Issue&Volume: January 30, 2020

Abstract: 

Background
 
In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed.
 
Methods
 
We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus.
 
Findings
 
The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues.
 
Interpretation
 
2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation.

DOI: 10.1016/S0140-6736(20)30251-8

编辑:小柯机器人

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