SARS-CoV-2 variants combining spike mutations and the absence of ORF8 may be more transmissible and require close monitoring.

SARS-CoV-2 variants combining spike mutations and the absence of ORF8 may be more transmissible and require close monitoring.
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DOI:
10.1016/j.bbrc.2021.02.080
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发表时间:
2021-04-23
影响因子:
3.1
通讯作者:
Pereira F
Pereira F
中科院分区:
生物学4区
文献类型:
--
作者:
Pereira F

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SARS-CoV-2关注变体202012/01(VOC-202012/01)出现在英格兰东南部,并迅速蔓延到世界各地。这种变体被认为更具传播性,所有的注意力都集中在其穗突变上。然而,VOC-202012/01也有一个突变(Q27 stop),截断了ORF 8,这是一种可能的免疫逃避蛋白。ORF 8的去除改变了疾病的临床开始,这可能会影响病毒的传播性。在这里,我提供了一个详细的分析,所有报告的ORF 8缺陷谱系中发现的相关尖峰突变的背景下,确定在231,433 SARS-CoV-2基因组。我发现了19个ORF 8无义突变,其中大多数发生在基因的5'端。ORF 8缺陷谱系是罕见的,占测序基因组的0.67%。尽管如此,我还是确定了两组最近出现并在不同国家传播的相关序列。D 614 G突变在大多数ORF缺失的家系中普遍存在。尽管不太常见,但HV 69 - 70 del和L5 F刺突突变发生在六种不同ORF 8无义突变的背景下。我还证实VOC-202012/01是迄今为止报道的具有更多尖峰突变的ORF 8缺陷变体,尽管其他变体可能具有多达6个尖峰突变,其中一些具有推定的生物学相关性。总体而言,这些结果表明,监测ORF 8缺陷谱系对于COVID-19大流行的进展非常重要,特别是当与相关尖峰突变相关时。
The SARS-CoV-2 Variant of Concern 202012/01 (VOC-202012/01) emerged in southeast England and rapidly spread worldwide. This variant is believed to be more transmissible, with all attention being given to its spike mutations. However, VOC-202012/01 has also a mutation (Q27stop) that truncates the ORF8, a likely immune evasion protein. Removal of ORF8 changes the clinical outset of the disease, which may affect the virus transmissibility. Here I provide a detailed analysis of all reported ORF8-deficient lineages found in the background of relevant spike mutations, identified among 231,433 SARS-CoV-2 genomes. I found 19 ORF8 nonsense mutations, most of them occurring in the 5’ half of the gene. The ORF8-deficient lineages were rare, representing 0.67% of sequenced genomes. Nevertheless, I identified two clusters of related sequences that emerged recently and spread in different countries. The widespread D614G spike mutation was found in most ORF-deficient lineages. Although less frequent, HV69-70del and L5F spike mutations occurred in the background of six different ORF8 nonsense mutations. I also confirmed that VOC-202012/01 is the ORF8-deficient variant with more spike mutations reported to date, although other variants could have up to six spike mutations, some of putative biological relevance. Overall, these results suggest that monitoring ORF8-deficient lineages is important for the progression of the COVID-19 pandemic, particularly when associated with relevant spike mutations.
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