SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity.

SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity.
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DOI:
10.1038/s41467-020-19808-4
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发表时间:
2020-11-26
影响因子:
16.6
通讯作者:
Choe H
Choe H
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Zhang L;Jackson CB;Mou H;Ojha A;Peng H;Quinlan BD;Rangarajan ES;Pan A;Vanderheiden A;Suthar MS;Li W;Izard T;Rader C;Farzan M;Choe H

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具有刺突蛋白D 614 G突变的SARS-CoV-2变体现在在全球占主导地位。因此,我们比较了突变的S蛋白(SG 614)与原始(SD 614)的特性。我们在这里报告携带SG 614的假病毒比携带SD 614的假病毒更有效地进入ACE 2表达细胞。这种增加的进入与较少的S1-结构域脱落和较高的S-蛋白掺入病毒体相关。用SARS-CoV-2 M、N、E和S蛋白产生的病毒样颗粒也得到了类似的结果。然而,D 614 G不改变S蛋白与ACE 2的结合或假病毒的中和敏感性。因此,D 614 G可以通过将更多功能性S蛋白组装到病毒体中来增加感染性。具有刺突蛋白D 614 G突变的SARS-CoV-2变体目前在全球占主导地位。在此,Zhang等人假设D 614 G变体可以通过增加病毒粒子上的S蛋白丰度来增加感染性,因为携带S-G614的假病毒比携带S-D 614的假病毒掺入更高量的S蛋白并且更有效地进入细胞。
SARS-CoV-2 variants with spike (S)-protein D614G mutations now predominate globally. We therefore compare the properties of the mutated S protein (SG614) with the original (SD614). We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than those with SD614. This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. Similar results are obtained with virus-like particles produced with SARS-CoV-2 M, N, E, and S proteins. However, D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion. SARS-CoV-2 variants with spike (S)-protein D614G mutations currently predominate globally. Here, Zhang et al. hypothesize that D614G variant may increase infectivity by increasing S protein abundance on the virion since pseudoviruses carrying S-G614 incorporate higher amounts of S protein and enter cells more efficiently than those carrying S-D614.
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