Positive selection as a key player for SARS-CoV-2 pathogenicity: Insights into ORF1ab, S and E genes.
Positive selection as a key player for SARS-CoV-2 pathogenicity: Insights into ORF1ab, S and E genes.
复制标题
DOI：
10.1016/j.virusres.2021.198472
复制
发表时间：
2021-09
期刊：
影响因子：
5
通讯作者：
El-Hadidi M
中科院分区：
文献类型：
--
作者：
Emam M;Oweda M;Antunes A;El-Hadidi M
人类β-冠状病毒SARS-CoV-2疫情于2019年12月下旬在中国武汉开始。它导致Covid-19疾病已成为流行病。已知的5种人类β-冠状病毒中，每一种都有4种主要的结构蛋白（E、M、N和S）和16种由ORF 1a和ORF 1b共同编码的非结构蛋白（ORF 1ab），这些蛋白与病毒的致病性和感染性有关。在这里，我们对这六个基因进行了详细的正选择分析，这些基因来自四种先前已知的人类β-冠状病毒和38个SARS-CoV-2基因组，以使用最大似然方法评估适应性进化的特征。我们的研究结果表明，三个基因（E，S和ORF 1ab基因）在人类β-冠状病毒中处于强的正选择特征下，影响位于功能重要蛋白质结构域的密码子。E蛋白编码基因在Asp 66和Ser 68两个位点显示出正选择的特征，这两个位点位于一个假定的跨膜α螺旋结构域C-末端部分，该结构域优先由亲水残基组成。这种Asp和Ser位点取代（亲水残基）增加了SARS-CoV-2中跨膜结构域的稳定性。此外，在刺突蛋白（S）的S1 N端结构域中也发现了替换，它们都位于S蛋白的表面，表明它们在病毒的传播和存活中的重要性。此外，在三个SARS-CoV-2非结构蛋白（NSP 1，NSP 3，NSP 16）中检测到强阳性选择的证据，这些蛋白由ORF 1ab编码，并在抑制宿主翻译机制，病毒复制和转录以及抑制宿主免疫反应中起重要作用。这些结果对于评估SARS-CoV-2编码蛋白中正选择的作用具有重要意义，这将有助于更好地了解病毒的毒性致病性，并可能为药物或疫苗策略设计确定靶标
The human β-coronavirus SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China. It causes Covid-19 disease which has become pandemic. Each of the five-known human β-coronaviruses has four major structural proteins (E, M, N and S) and 16 non-structural proteins encoded by ORF1a and ORF1b together (ORF1ab) that are involved in virus pathogenicity and infectivity. Here, we performed detailed positive selection analyses for those six genes among the four previously known human β-coronaviruses and within 38 SARS-CoV-2 genomes to assess signatures of adaptive evolution using maximum likelihood approaches. Our results suggest that three genes (E, S and ORF1ab genes) are under strong signatures of positive selection among human β-coronavirus, influencing codons that are located in functional important protein domains. The E protein-coding gene showed signatures of positive selection in two sites, Asp 66 and Ser 68, located inside a putative transmembrane α-helical domain C-terminal part, which is preferentially composed by hydrophilic residues. Such Asp and Ser sites substitutions (hydrophilic residues) increase the stability of the transmembrane domain in SARS-CoV-2. Moreover, substitutions in the spike (S) protein S1 N-terminal domain have been found, all of them were located on the S protein surface, suggesting their importance in viral transmissibility and survival. Furthermore, evidence of strong positive selection was detected in three of the SARS-CoV-2 nonstructural proteins (NSP1, NSP3, NSP16), which are encoded by ORF1ab and play vital roles in suppressing host translation machinery, viral replication and transcription and inhibiting the host immune response. These results are insightful to assess the role of positive selection in the SARS-CoV-2 encoded proteins, which will allow to better understand the virulent pathogenicity of the virus and potentially identifying targets for drug or vaccine strategy design
登录
查看更多内容
影响因子：
10.7
作者：
Castresana, J
通讯作者：
Castresana, J
影响因子：
6.7
作者：
Huang C;Lokugamage KG;Rozovics JM;Narayanan K;Semler BL;Makino S
通讯作者：
Makino S
影响因子：
11.4
作者：
Li, WH;Zhang, CS;Sui, JH;Kuhn, JH;Moore, MJ;Luo, SW;Wong, SK;Huang, IC;Xu, KM;Vasilieva, N;Murakami, A;He, YQ;Marasco, WA;Guan, Y;Choe, HY;Farzan, M
通讯作者：
Farzan, M
影响因子：
28.3
作者：
Gorbalenya, Alexander E.;Baker, Susan C.;Ziebuhr, John
通讯作者：
Ziebuhr, John
影响因子：
9.5
作者：
Hubisz, Melissa J.;Pollard, Katherine S.;Siepel, Adam
通讯作者：
Siepel, Adam