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对来自土耳其患者的 SARS-CoV-2 分离株进行基因组特征分析显示,刺突蛋白和 nsp12 蛋白存在新型突变。

Genomic characterization of SARS-CoV-2 isolates from patients in Turkey reveals the presence of novel mutations in spike and nsp12 proteins.

机构信息

Division of Medical Virology, Department of Medical Microbiology, Faculty of Medicine, Gazi University, Ankara, Turkey.

Department of Infectious Diseases and Medical Microbiology, Faculty of Medicine, Gazi University, Ankara, Turkey.

出版信息

J Med Virol. 2021 Oct;93(10):6016-6026. doi: 10.1002/jmv.27188. Epub 2021 Jul 16.


DOI:10.1002/jmv.27188
PMID:34241906
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8426744/
Abstract

Novel mutations have been emerging in the genome of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2); consequently, the evolving of more virulent and treatment resistance strains have the potential to increase transmissibility and mortality rates. The characterization of full-length SARS-CoV-2 genomes is critical for understanding the origin and transmission pathways of the virus, as well as identifying mutations that affect the transmissibility and pathogenicity of the virus. We present an analysis of the mutation pattern and clade distribution of full-length SARS-CoV-2 genome sequences obtained from specimens tested at Gazi University Medical Virology Laboratory. Viral RNA was extracted from nasopharyngeal specimens. Next-generation sequencing libraries were prepared and sequenced on Illumina iSeq 100 platform. Raw sequencing data were processed to obtain full-length genome sequences and variant calling was performed to analyze amino acid changes. Clade distribution was determined to understand the phylogenetic background in relation to global data. A total of 293 distinct mutations were identified, of which 152 missense, 124 synonymous, 12 noncoding, and 5 deletions. The most frequent mutations were P323L (nsp12), D614G (ORF2/S), and 2421C>T (5'-untranslated region) found simultaneously in all sequences. Novel mutations were found in nsp12 (V111A, H133R, Y453C, M626K) and ORF2/S (R995G, V1068L). Nine different Pangolin lineages were detected. The most frequently assigned lineage was B.1.1 (17 sequences), followed by B.1 (7 sequences) and B.1.1.36 (3 sequences). Sequence information is essential for revealing genomic diversity. Mutations might have significant functional implications and analysis of these mutations provides valuable information for therapeutic and vaccine development studies. Our findings point to the introduction of the virus into Turkey through various sources and the subsequent spread of several key variants.

摘要

新型突变不断出现在严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的基因组中;因此,更具毒性和治疗抗性的菌株的进化有可能增加传染性和死亡率。对全长 SARS-CoV-2 基因组序列的特征分析对于了解病毒的起源和传播途径以及确定影响病毒传染性和致病性的突变至关重要。我们对从加济大学医学病毒学实验室检测的标本中获得的全长 SARS-CoV-2 基因组序列的突变模式和进化枝分布进行了分析。从鼻咽标本中提取病毒 RNA。制备下一代测序文库并在 Illumina iSeq 100 平台上进行测序。对原始测序数据进行处理以获得全长基因组序列,并进行变异调用以分析氨基酸变化。确定进化枝分布以了解与全球数据相关的系统发育背景。共鉴定出 293 个不同的突变,其中 152 个错义突变,124 个同义突变,12 个非编码突变和 5 个缺失突变。最常见的突变是同时在所有序列中发现的 nsp12 上的 P323L(nsp12)、ORF2/S 上的 D614G(ORF2/S)和 5'-非翻译区的 2421C>T。在 nsp12(V111A、H133R、Y453C、M626K)和 ORF2/S(R995G、V1068L)上发现了新的突变。检测到 9 种不同的穿山甲谱系。最常分配的谱系是 B.1.1(17 个序列),其次是 B.1(7 个序列)和 B.1.1.36(3 个序列)。序列信息对于揭示基因组多样性至关重要。突变可能具有重要的功能意义,对这些突变的分析为治疗和疫苗开发研究提供了有价值的信息。我们的研究结果表明,该病毒通过多种来源传入土耳其,并随后传播了几种关键变体。

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本文引用的文献

[1]
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BMC Bioinformatics. 2022-4-19

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In-Silico analysis reveals lower transcription efficiency of C241T variant of SARS-CoV-2 with host replication factors MADP1 and hnRNP-1.

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Current mutatome of SARS-CoV-2 in Turkey reveals mutations of interest.

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SARS-CoV-2 viral load is associated with increased disease severity and mortality.

Nat Commun. 2020-10-30

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