Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7.
Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7.
复制标题
DOI：
10.1016/j.celrep.2021.109292
复制
发表时间：
2021-06-29
期刊：
影响因子：
8.8
通讯作者：
Gupta RK
中科院分区：
文献类型：
--
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
我们报告了严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）在多个独立谱系中的尖峰ΔH69/V70，通常发生在获得受体结合基序替换（如N439 K和Y 453 F）后，已知这些基序增加与ACE 2受体的结合亲和力并赋予抗体逃逸。在体外，我们表明，尽管ΔH69/V70本身不是抗体逃避机制，但它增加了与裂解的刺突掺入病毒体增强相关的感染性。ΔH69/V70能够通过增加刺突掺入部分挽救已经获得N439 K和Y 453 F逃逸突变的刺突蛋白的感染性。此外，α变体B.1.1.7加标物中H69和V70残基的替换（其中ΔH69/V70天然存在）会损害B.1.1.7加标物假型病毒的加标物掺入和进入效率。α变体B.1.1.7刺突介导比野生型Wuhan-1 D 614 G更快的细胞-细胞融合动力学，依赖于ΔH69/V70。因此，由于ΔH69/V70补偿了损害感染性的免疫逃逸突变，因此有必要继续监测具有功能效应的缺失。加标ΔH69/V70不会使抗体逃逸加标ΔH69/V70增加裂解的S2和加标感染性B.1.1.7需要ΔH69/V70进行有效裂解的加标掺入，而感染性B.1.1.7加标需要ΔH69/V70进行快速合胞体形成Meng et al.报告称，SARS-CoV-2尖峰ΔH69/V70多次出现。该缺失增加了与病毒体中增加的切割尖峰相关的进入效率，并且可以补偿感染性的损失。B.1.1.7加标需要ΔH69/V70以实现有效的细胞进入和细胞-细胞融合活性。
We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of receptor binding motif replacements such as N439K and Y453F, known to increase binding affinity to the ACE2 receptor and confer antibody escape. In vitro, we show that, although ΔH69/V70 itself is not an antibody evasion mechanism, it increases infectivity associated with enhanced incorporation of cleaved spike into virions. ΔH69/V70 is able to partially rescue infectivity of spike proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of the H69 and V70 residues in the Alpha variant B.1.1.7 spike (where ΔH69/V70 occurs naturally) impairs spike incorporation and entry efficiency of the B.1.1.7 spike pseudotyped virus. Alpha variant B.1.1.7 spike mediates faster kinetics of cell-cell fusion than wild-type Wuhan-1 D614G, dependent on ΔH69/V70. Therefore, as ΔH69/V70 compensates for immune escape mutations that impair infectivity, continued surveillance for deletions with functional effects is warranted. Spike ΔH69/V70 does not confer escape from antibodies Spike ΔH69/V70 increases cleaved S2 and spike infectivity B.1.1.7 requires ΔH69/V70 for efficient cleaved spike incorporation and infectivity B.1.1.7 spike requires ΔH69/V70 for rapid syncytium formation Meng et al. report that the SARS-CoV-2 spike ΔH69/V70 has arisen multiple times. The deletion increases entry efficiency associated with increased cleaved spike in virions and can compensate for loss of infectivity. The B.1.1.7 spike requires ΔH69/V70 for efficient cell entry and cell-cell fusion activity.
登录
查看更多内容
影响因子：
16
作者：
Huston NC;Wan H;Strine MS;de Cesaris Araujo Tavares R;Wilen CB;Pyle AM
通讯作者：
Pyle AM
影响因子：
10.7
作者：
Minh BQ;Nguyen MA;von Haeseler A
通讯作者：
von Haeseler A
影响因子：
30.3
作者：
Case, James Brett;Rothlauf, Paul W.;Whelan, Sean P. J.
通讯作者：
Whelan, Sean P. J.
影响因子：
8.8
作者：
Hoffmann M;Zhang L;Krüger N;Graichen L;Kleine-Weber H;Hofmann-Winkler H;Kempf A;Nessler S;Riggert J;Winkler MS;Schulz S;Jäck HM;Pöhlmann S
通讯作者：
Pöhlmann S
影响因子：
64.8
作者：
通讯作者：
--