Quasi-species nature and differential gene expression of severe acute respiratory syndrome coronavirus 2 and phylogenetic analysis of a novel Iranian strain
Quasi-species nature and differential gene expression of severe acute respiratory syndrome coronavirus 2 and phylogenetic analysis of a novel Iranian strain
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DOI：
10.1016/j.meegid.2020.104556
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发表时间：
2020-11-01
影响因子：
3.2
通讯作者：
Peters, Jonathan R.
中科院分区：
文献类型：
--
作者：
Ghorbani, Abozar;Samarfard, Samira;Peters, Jonathan R.
一种与严重急性呼吸综合征病毒（SARS-CoV-2）相关的新型冠状病毒是导致COVID-19大流行的病原体。尽管最近对SARS-CoV-2基因组的基因突变进行了研究，但其在宿主间水平的转录组遗传多态性和基于每个开放阅读框（ORF）的病毒基因表达水平仍不清楚。利用现有的高通量测序（High Throughput Sequencing， HTS）数据，基于SARS-CoV-2感染的人转录组学数据，本研究在宿主间水平上绘制了SARS-CoV-2病毒群体中单核苷酸多态性（SNP）热点的高分辨率图谱。收集了来自COVID-19感染患者的四个咽拭子样本，并从SRA NCBI中检索了RNA-Seq，以检测整个SARS-CoV-2基因组群体中的21个snp和一个替换。在病毒转录本上鉴定出22个可能导致该病毒宿主间遗传多样性的RNA修饰位点。此外，与其他SARS-CoV-2 ORF相比，N ORF的典型基因组rna在转录组学数据和逆转录酶定量PCR中表达量更高，表明该ORF在病毒复制或病毒周期中的其他主要功能中具有重要作用。基于全基因组的系统发育和祖先序列分析显示，SARS-CoV-2可能来源于SARS-CoV与蝙蝠sars样冠状病毒之间的重组事件。对来自包括伊朗在内的不同地区的分离株的祖先分析表明，它们有共同的中国祖先。这些结果表明，潜在的宿主间遗传变异对SARS-COV-2的进化和病毒准物种的形成至关重要。本研究发现的RNA修饰可能导致SARS-CoV-2多蛋白、刺突蛋白、ORF8产物和核衣壳(N)蛋白的氨基酸序列改变，为进一步了解突变在SARS-CoV-2生命周期和致病性中的功能影响提供了新的思路。
A novel coronavirus related to severe acute respiratory syndrome virus, (SARS-CoV-2) is the causal agent of the COVID-19 pandemic. Despite the genetic mutations across the SARS-CoV-2 genome being recently investigated, its transcriptomic genetic polymorphisms at inter-host level and the viral gene expression level based on each Open Reading Frame (ORF) remains unclear. Using available High Throughput Sequencing (HTS) data and based on SARS-CoV-2 infected human transcriptomic data, this study presents a high-resolution map of SARS-CoV-2 single nucleotide polymorphism (SNP) hotspots in a viral population at inter-host level. Four throat swab samples from COVID-19 infected patients were pooled, with RNA-Seq read retrieved from SRA NCBI to detect 21 SNPs and a replacement across the SARS-CoV-2 genomic population. Twenty-two RNA modification sites on viral transcripts were identified that may cause inter-host genetic diversity of this virus. In addition, the canonical genomic RNAs of N ORF showed higher expression in transcriptomic data and reverse transcriptase quantitative PCR compared to other SARS-CoV-2 ORFs, indicating the importance of this ORF in virus replication or other major functions in virus cycle. Phylogenetic and ancestral sequence analyses based on the entire genome revealed that SARS-CoV-2 is possibly derived from a recombination event between SARS-CoV and Bat SARS-like CoV. Ancestor analysis of the isolates from different locations including Iran suggest shared Chinese ancestry. These results propose the importance of potential inter-host level genetic variations to the evolution of SARS-COV-2, and the formation of viral quasi-species. The RNA modifications discovered in this study may cause amino acid sequence changes in polyprotein, spike protein, product of ORF8 and nucleocapsid (N) protein, suggesting further insights to understanding the functional impacts of mutations in the life cycle and pathogenicity of SARS-CoV-2.