The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection.
The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection.
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DOI：
10.1186/s13059-023-02881-5
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发表时间：
2023-03-13
期刊：
影响因子：
12.3
通讯作者：
中科院分区：
文献类型：
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作者：
SARS-CoV-2的突变景观在优势病毒基因组序列和次要基因组变异群体中变化。在COVID-19大流行期间，基因组中的早期替换是刺突蛋白中的D 614 G变化，与传播性增加相关。具有D 614 G的基因组伴随着病毒聚合酶（NSP 12）中的P323 L取代。然而，P323 L被认为没有受到强烈的选择压力。P323 L/D 614 G取代的人口调查显示，在遏制阶段和早期激增阶段的第一波期间迅速出现。这些取代出现于次要基因组变异，其成为显性病毒基因组序列。使用SARS-CoV-2进行体内和体外研究，其中P323和D 614在显性基因组序列中，L323和G614在次要变异群体中。在感染过程中，L323被快速选择进入显性病毒基因组序列，但G614没有。反向遗传学用于创建具有相同遗传背景的两种病毒（P323或L323）。与P323相比，L323显示出更大丰度的病毒RNA和蛋白质以及更小的空斑形态。这些数据表明，P323 L是一个重要的贡献，在出现的变种与传输的优势。对病毒种群的序列分析表明，有可能根据跟踪微小变异基因组的频率来预测新变异的出现。预测全球范围内出现的SARS-CoV-2变异的能力可能有助于评估医学对策和非药物干预措施。在线版本包含补充材料，可通过10.1186/s13059-023-02881-5获得。
The mutational landscape of SARS-CoV-2 varies at the dominant viral genome sequence and minor genomic variant population. During the COVID-19 pandemic, an early substitution in the genome was the D614G change in the spike protein, associated with an increase in transmissibility. Genomes with D614G are accompanied by a P323L substitution in the viral polymerase (NSP12). However, P323L is not thought to be under strong selective pressure. Investigation of P323L/D614G substitutions in the population shows rapid emergence during the containment phase and early surge phase during the first wave. These substitutions emerge from minor genomic variants which become dominant viral genome sequence. This is investigated in vivo and in vitro using SARS-CoV-2 with P323 and D614 in the dominant genome sequence and L323 and G614 in the minor variant population. During infection, there is rapid selection of L323 into the dominant viral genome sequence but not G614. Reverse genetics is used to create two viruses (either P323 or L323) with the same genetic background. L323 shows greater abundance of viral RNA and proteins and a smaller plaque morphology than P323. These data suggest that P323L is an important contribution in the emergence of variants with transmission advantages. Sequence analysis of viral populations suggests it may be possible to predict the emergence of a new variant based on tracking the frequency of minor variant genomes. 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. The online version contains supplementary material available at 10.1186/s13059-023-02881-5.
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使用LETRS（一种生物信息学工具）分析细胞培养，动物模型和临床样品中SARS-COV-2已知和新型亚基因组mRNA，以识别唯一的序列标识符。
影响因子：
9.2
作者：
通讯作者：
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影响因子：
4.4
作者：
Morelli MJ;Wright CF;Knowles NJ;Juleff N;Paton DJ;King DP;Haydon DT
通讯作者：
Haydon DT
DOI：
10.1126/science.abe8499
发表时间：
2020-12-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hou YJ;Chiba S;Halfmann P;Ehre C;Kuroda M;Dinnon KH 3rd;Leist SR;Schäfer A;Nakajima N;Takahashi K;Lee RE;Mascenik TM;Graham R;Edwards CE;Tse LV;Okuda K;Markmann AJ;Bartelt L;de Silva A;Margolis DM;Boucher RC;Randell SH;Suzuki T;Gralinski LE;Kawaoka Y;Baric RS
通讯作者：
Baric RS
SARS-COV-2内部多样性和传播。
DOI：
10.1126/science.abg0821
发表时间：
2021-04-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lythgoe KA;Hall M;Ferretti L;de Cesare M;MacIntyre-Cockett G;Trebes A;Andersson M;Otecko N;Wise EL;Moore N;Lynch J;Kidd S;Cortes N;Mori M;Williams R;Vernet G;Justice A;Green A;Nicholls SM;Ansari MA;Abeler-Dörner L;Moore CE;Peto TEA;Eyre DW;Shaw R;Simmonds P;Buck D;Todd JA;Oxford Virus Sequencing Analysis Group (OVSG);Connor TR;Ashraf S;da Silva Filipe A;Shepherd J;Thomson EC;COVID-19 Genomics UK (COG-UK) Consortium;Bonsall D;Fraser C;Golubchik T
通讯作者：
Golubchik T
DOI：
10.1099/jgv.0.001584
发表时间：
2021-04
期刊：
The Journal of general virology
影响因子：
--
作者：
Peacock TP;Penrice-Randal R;Hiscox JA;Barclay WS
通讯作者：
Barclay WS