D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization.
D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization.
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D614G棘突突变增加SARS CoV-2对中和的易感性。
DOI：
10.1016/j.chom.2020.11.012
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发表时间：
2021-01-13
影响因子：
30.3
通讯作者：
Montefiori DC
中科院分区：
文献类型：
--
作者：
Weissman D;Alameh MG;de Silva T;Collini P;Hornsby H;Brown R;LaBranche CC;Edwards RJ;Sutherland L;Santra S;Mansouri K;Gobeil S;McDanal C;Pardi N;Hengartner N;Lin PJC;Tam Y;Shaw PA;Lewis MG;Boesler C;Şahin U;Acharya P;Haynes BF;Korber B;Montefiori DC
严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 刺突蛋白在大流行早期获得了 D614G 突变，具有更强的传染性，目前是全球主导形式。为了确定 D614G 是否也可能介导可能损害疫苗功效的中和逃逸，评估了来自刺突免疫小鼠、非人灵长类动物和人类的血清对携带 D614 或 G614 刺突的假病毒的中和作用。在所有情况下，G614 假病毒对中和的敏感性稍高。 G614 假病毒也更容易被受体结合域 (RBD) 单克隆抗体和感染这两种病毒的人的恢复期血清中和。负染色电子显微镜显示 G614 刺突中 1-RBD“向上”构象的百分比较高，表明表位暴露增加是增强中和脆弱性的机制。基于这些发现，D614G 突变预计不会成为当前疫苗开发的障碍。来自接种 SARS-CoV-2 疫苗的小鼠、NHP 和人类以及恢复期患者的血清以及受体结合域 (RBD) 特异性单克隆抗体可以比原始 D614 版本更高的水平中和广泛传播的含 G614 病毒。结构数据表明，G614 刺突处于更开放的构象，具有扩展的 RBD。
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein acquired a D614G mutation early in the pandemic that confers greater infectivity and is now the globally dominant form. To determine whether D614G might also mediate neutralization escape that could compromise vaccine efficacy, sera from spike-immunized mice, nonhuman primates, and humans were evaluated for neutralization of pseudoviruses bearing either D614 or G614 spike. In all cases, the G614 pseudovirus was moderately more susceptible to neutralization. The G614 pseudovirus also was more susceptible to neutralization by receptor-binding domain (RBD) monoclonal antibodies and convalescent sera from people infected with either form of the virus. Negative stain electron microscopy revealed a higher percentage of the 1-RBD “up” conformation in the G614 spike, suggesting increased epitope exposure as a mechanism of enhanced vulnerability to neutralization. Based on these findings, the D614G mutation is not expected to be an obstacle for current vaccine development. Serum from SARS-CoV-2 spike-vaccinated mice, NHPs and humans, and convalescent patients, along with receptor-binding domain (RBD)-specific monoclonal antibodies neutralize the widespread G614-containing virus at greater levels than the original D614 version. Structural data demonstrate that the G614 spike is in a more open conformation with extended RBDs.
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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
影响因子：
4.6
作者：
Isabel, Sandra;Grana-Miraglia, Lucia;Poutanen, Susan M.
通讯作者：
Poutanen, Susan M.
影响因子：
16.8
作者：
Henderson R;Edwards RJ;Mansouri K;Janowska K;Stalls V;Gobeil SMC;Kopp M;Li D;Parks R;Hsu AL;Borgnia MJ;Haynes BF;Acharya P
通讯作者：
Acharya P
影响因子：
12.4
作者：
Freyn, Alec W.;da Silva, Jamile Ramos;Nachbagauer, Raffael
通讯作者：
Nachbagauer, Raffael
影响因子：
64.5
作者：
Korber, Bette;Fischer, Will M.;Montefiori, David C.
通讯作者：
Montefiori, David C.