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《Nature，11月26日，SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2020-12-22

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

    Lizhou Zhang, Cody B. Jackson, Huihui Mou, Amrita Ojha, Haiyong Peng, Brian D. Quinlan, Erumbi S. Rangarajan, Andi Pan, Abigail Vanderheiden, Mehul S. Suthar, Wenhui Li, Tina Izard, Christoph Rader, Michael Farzan & Hyeryun Choe

    Nature Communications volume 11, Article number: 6013 (2020)

    Abstract

    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.

  • 原文来源：https://www.nature.com/articles/s41467-020-19808-4
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  • 《Nature，10月26日，Spike mutation D614G alters SARS-CoV-2 fitness》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-11-17
    • Spike mutation D614G alters SARS-CoV-2 fitness Jessica A. Plante, Yang Liu, Jianying Liu, Hongjie Xia, Bryan A. Johnson, Kumari G. Lokugamage, Xianwen Zhang, Antonio E. Muruato, Jing Zou, Camila R. Fontes-Garfias, Divya Mirchandani, Dionna Scharton, John P. Bilello, Zhiqiang Ku, Zhiqiang An, Birte Kalveram, Alexander N. Freiberg, Vineet D. Menachery, Xuping Xie, Kenneth S. Plante, Scott C. Weaver & Pei-Yong Shi Nature (2020) Abstract A spike protein mutation D614G became dominant in SARS-CoV-2 during the COVID-19 pandemic1,2. However, the impact on viral spread and vaccine efficacy remains to be defined. Here, we engineer the D614G mutation in the USA-WA1/2020 strain and characterize its effect. D614G enhances replication on human lung epithelial cells and primary human airway tissues through an improved infectivity of virions. Hamsters infected with the G614 variant produced higher infectious titers in the nasal washes and trachea, but not lungs, confirming clinical evidence that the D614G mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increases transmission. Sera from D614-infected hamsters exhibit modestly higher neutralization titers against G614 virus than against D614 virus, indicating that (i) the mutation may not reduce the ability of vaccines in clinical trials to protect against COVID-19 and (ii) therapeutic antibodies should be tested against the circulating G614 virus. Together with clinical findings, our work underscores the importance of this mutation in viral spread, vaccine efficacy, and antibody therapy.
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  • 《Cell，11月18日，Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-12-21
    • Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity Erik Volz 13 Verity Hill John T. McCrone Emma C. Thomson Andrew Rambaut Thomas R. Connor Open AccessPublished:November 18, 2020DOI:https://doi.org/10.1016/j.cell.2020.11.020 Summary Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.
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