Rapid selection of P323L in the SARS-CoV-2 polymerase (NSP12) in humans and non-human primate models and confers a large plaque phenotype
Rapid selection of P323L in the SARS-CoV-2 polymerase (NSP12) in humans and non-human primate models and confers a large plaque phenotype
复制标题
在人类和非人类灵长类动物模型中，快速选择 SARS-CoV-2 聚合酶 (NSP12) 中的 P323L，并赋予大斑块表型
DOI：
10.1101/2021.12.23.474030
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Dong X
中科院分区：
文献类型：
--
作者：
Dong X
SARS-CoV-2的突变格局在优势病毒基因组序列和次要基因组变异群体中都有所不同。与传递性相关的早期变化是刺突蛋白中的D614G取代。这似乎伴随着病毒聚合酶（NSP12）的P323L取代，但后者的变化不是在强选择压力下发生的。对人群中P323L/D614G变化的调查显示，在英国第一波疫情的遏制阶段和早期激增阶段，P323L/D614G迅速出现。这种快速的替换是从次要的基因组变异到成为优势病毒基因组序列的一部分。在COVID-19的非人灵长类动物模型中，使用P323和D614在优势基因组序列中启动病毒，323L和614G在次要变异群体中启动病毒，观察到323L和614G快速出现，而不是614G。在细胞培养中，在NSP12中含有323L的重组病毒比含有P323的重组病毒具有更大的斑块大小。这些数据表明，在群体水平上，基于跟踪次要变异基因组的分布和频率，而不是仅仅关注于提供显性病毒基因组序列的信息，例如共识水平报告，有可能预测新变异的出现。在全球范围内预测新出现的SARS-CoV-2变体的能力可能有助于评估医疗对策和非药物干预措施。
The mutational landscape of SARS-CoV-2 varies at both the dominant viral genome sequence and minor genomic variant population. An early change associated with transmissibility was the D614G substitution in the spike protein. This appeared to be accompanied by a P323L substitution in the viral polymerase (NSP12), but this latter change was not under strong selective pressure. Investigation of P323L/D614G changes in the human population showed rapid emergence during the containment phase and early surge phase of wave 1 in the UK. This rapid substitution was from minor genomic variants to become part of the dominant viral genome sequence. A rapid emergence of 323L but not 614G was observed in a non-human primate model of COVID-19 using a starting virus with P323 and D614 in the dominant genome sequence and 323L and 614G in the minor variant population. In cell culture, a recombinant virus with 323L in NSP12 had a larger plaque size than the same recombinant virus with P323. These data suggest that it may be possible to predict the emergence of a new variant based on tracking the distribution and frequency of minor variant genomes at a population level, rather than just focusing on providing information on the dominant viral genome sequence e.g., consensus level reporting. The ability to predict an emerging variant of SARS-CoV-2 in the global landscape may aid in the evaluation of medical countermeasures and non-pharmaceutical interventions.
影响因子：
11.4
作者：
Caly, Leon;Druce, Julian;Catton, Mike G.
通讯作者：
Catton, Mike G.
影响因子：
56.9
作者：
Kraemer, Moritz U. G.;Hill, Verity;Ruis, Christopher;Dellicour, Simon;Bajaj, Sumali;McCrone, John T.;Baele, Guy;Parag, Kris V.;Battle, Anya Lindstrom;Gutierrez, Bernardo;Jackson, Ben;Colquhoun, Rachel;O'Toole, Aine;Klein, Brennan;Vespignani, Alessandro;Volz, Erik;Faria, Nuno R.;Aanensen, David M.;Loman, Nicholas J.;du Plessis, Louis;Cauchemez, Simon;Rambaut, Andrew;Scarpino, Samuel V.;Pybus, Oliver G.
通讯作者：
Pybus, Oliver G.