Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus

Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus
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DOI:
10.1016/j.cell.2020.06.043
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发表时间:
2020-08-20
期刊:
影响因子:
64.5
通讯作者:
Montefiori, David C.
Montefiori, David C.
中科院分区:
生物学1区
文献类型:
--
作者:
Korber, Bette;Fischer, Will M.;Montefiori, David C.

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携带刺突蛋白氨基酸变化D 614 G的SARS-CoV-2变体已成为全球大流行中最流行的形式。对变异频率的动态跟踪揭示了G614在多个地理级别(国家、地区和市政)的重复性增加模式。这种转变甚至发生在地方流行病中,其中原始D 614形式在引入G614变体之前已经很好地建立。这种模式的一致性在统计学上非常显著,表明G614变体可能具有适应性优势。我们发现G614变异体作为假型病毒体生长至更高滴度。在感染个体中,G614与较低的RT-PCR循环阈值相关,提示较高的上呼吸道病毒载量,但与疾病严重程度增加无关。这些发现阐明了对于理解病毒的机制重要的变化,并支持继续监测刺突突变,以帮助开发免疫干预措施。
A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional, and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to a higher titer as pseudotyped virions. In infected individuals, G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, but not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus and support continuing surveillance of Spike mutations to aid with development of immunological interventions.