The N501Y spike substitution enhances SARS-CoV-2 infection and transmission.
The N501Y spike substitution enhances SARS-CoV-2 infection and transmission.
复制标题
DOI：
10.1038/s41586-021-04245-0
复制
发表时间：
2022-03
期刊：
影响因子：
64.8
通讯作者：
Weaver SC
中科院分区：
文献类型：
--
作者：
Liu Y;Liu J;Plante KS;Plante JA;Xie X;Zhang X;Ku Z;An Z;Scharton D;Schindewolf C;Widen SG;Menachery VD;Shi PY;Weaver SC
导致COVID-19大流行的SARS-CoV-2的B.1.1.7变种（也称为Alpha）于2020年夏天在英国出现。由于感染和/或传播效率的增加，这种变异的流行率迅速增加。α变体在其病毒基因组中包含19个非同义突变，包括与细胞受体相互作用介导感染和趋向性的刺突蛋白中的8个替换或缺失。在这里，使用反向遗传学方法，我们发现在8个单独的刺突蛋白替换中，只有N501Y在仓鼠模型和原代人气道上皮细胞的上呼吸道复制中获得一致的适应性增益。N501Y替代重现了α刺突蛋白中8个突变的增强病毒传播表型，表明它是α变异传播增加的主要决定因素。机制上，N501Y取代增加了病毒刺突蛋白对细胞受体的亲和力。正如其在巴西、南非和其他地方的趋同进化所表明的那样，我们的研究结果表明，N501Y替代是一种主要关注的适应性刺突突变。
The B.1.1.7 variant (also known as Alpha) of SARS-CoV-2, the cause of the COVID-19 pandemic, emerged in the UK in the summer of 2020. The prevalence of this variant increased rapidly owing to an increase in infection and/or transmission efficiency. The Alpha variant contains 19 nonsynonymous mutations across its viral genome, including 8 substitutions or deletions in the spike protein that interacts with cellular receptors to mediate infection and tropism. Here, using a reverse genetics approach, we show that of the 8 individual spike protein substitutions, only N501Y resulted in consistent fitness gains for replication in the upper airway in a hamster model as well as in primary human airway epithelial cells. The N501Y substitution recapitulated the enhanced viral transmission phenotype of the eight mutations in the Alpha spike protein, suggesting that it is a major determinant of the increased transmission of the Alpha variant. Mechanistically, the N501Y substitution increased the affinity of the viral spike protein for cellular receptors. As suggested by its convergent evolution in Brazil, South Africa and elsewhere, our results indicate that N501Y substitution is an adaptive spike mutation of major concern.
登录
查看更多内容
DOI：
10.1126/science.abc4730
发表时间：
2020-09-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gu H;Chen Q;Yang G;He L;Fan H;Deng YQ;Wang Y;Teng Y;Zhao Z;Cui Y;Li Y;Li XF;Li J;Zhang NN;Yang X;Chen S;Guo Y;Zhao G;Wang X;Luo DY;Wang H;Yang X;Li Y;Han G;He Y;Zhou X;Geng S;Sheng X;Jiang S;Sun S;Qin CF;Zhou Y
通讯作者：
Zhou Y
影响因子：
64.8
作者：
Plante JA;Liu Y;Liu J;Xia H;Johnson BA;Lokugamage KG;Zhang X;Muruato AE;Zou J;Fontes-Garfias CR;Mirchandani D;Scharton D;Bilello JP;Ku Z;An Z;Kalveram B;Freiberg AN;Menachery VD;Xie X;Plante KS;Weaver SC;Shi PY
通讯作者：
Shi PY
影响因子：
8.8
作者：
Meng B;Kemp SA;Papa G;Datir R;Ferreira IATM;Marelli S;Harvey WT;Lytras S;Mohamed A;Gallo G;Thakur N;Collier DA;Mlcochova P;COVID-19 Genomics UK (COG-UK) Consortium;Duncan LM;Carabelli AM;Kenyon JC;Lever AM;De Marco A;Saliba C;Culap K;Cameroni E;Matheson NJ;Piccoli L;Corti D;James LC;Robertson DL;Bailey D;Gupta RK
通讯作者：
Gupta RK
影响因子：
5.8
作者：
Carr, I. M.;Robinson, J. I.;Bonthron, D. T.
通讯作者：
Bonthron, D. T.
影响因子：
5.4
作者：
Coffey, Lark L.;Vignuzzi, Marco
通讯作者：
Vignuzzi, Marco