In vitro Characterization of Fitness and Convalescent Antibody Neutralization of SARS-CoV-2 Cluster 5 Variant Emerging in Mink at Danish Farms.

In vitro Characterization of Fitness and Convalescent Antibody Neutralization of SARS-CoV-2 Cluster 5 Variant Emerging in Mink at Danish Farms.
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DOI:
10.3389/fmicb.2021.698944
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发表时间:
2021
影响因子:
5.2
通讯作者:
Fomsgaard A
Fomsgaard A
中科院分区:
生物学2区
文献类型:
--
作者:
Lassaunière R;Fonager J;Rasmussen M;Frische A;Polacek C;Rasmussen TB;Lohse L;Belsham GJ;Underwood A;Winckelmann AA;Bollerup S;Bukh J;Weis N;Sækmose SG;Aagaard B;Alfaro-Núñez A;Mølbak K;Bøtner A;Fomsgaard A

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除人类外,严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 还可传播给仓鼠、猫、狗、水貂、雪貂、老虎、狮子、食蟹猴、恒河猴和树鼩等动物。其中,水貂尤其容易受到影响。事实上,欧洲和北美 10 个国家报告了毛皮养殖场的水貂感染 SARS-CoV-2。在丹麦,SARS-CoV-2 在水貂养殖场中迅速传播,并蔓延回人类,产生突变/缺失,其毒力和抗原性后果未知。在这里,我们描述了水貂相关的 SARS-CoV-2 变体(簇 5),其特征是相对于 Wuu-Hu-1 有 11 个氨基酸取代和 4 个氨基酸缺失。时间病毒滴定,以及基因组和亚基因组病毒 RNA 定量,证明了 Cluster 5 病毒在 Vero-E6 细胞系中的体外适应性适度减弱。在病毒微中和测定中评估了刺突蛋白中氨基酸变化所带来的潜在抗原性改变,包括三个取代(Y453F、I692V和M1229I)以及两个氨基酸残基69和70(ΔH69/V70)的丢失。与参考菌株相比,Cluster 5 变体在部分恢复期人类 COVID-19 样本中显示出中和作用降低。研究结果强调需要主动监测易感动物宿主中的 SARS-CoV-2 感染和病毒进化。
In addition to humans, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit to animals that include hamsters, cats, dogs, mink, ferrets, tigers, lions, cynomolgus macaques, rhesus macaques, and treeshrew. Among these, mink are particularly susceptible. Indeed, 10 countries in Europe and North America reported SARS-CoV-2 infection among mink on fur farms. In Denmark, SARS-CoV-2 spread rapidly among mink farms and spilled-over back into humans, acquiring mutations/deletions with unknown consequences for virulence and antigenicity. Here we describe a mink-associated SARS-CoV-2 variant (Cluster 5) characterized by 11 amino acid substitutions and four amino acid deletions relative to Wuhan-Hu-1. Temporal virus titration, together with genomic and subgenomic viral RNA quantitation, demonstrated a modest in vitro fitness attenuation of the Cluster 5 virus in the Vero-E6 cell line. Potential alterations in antigenicity conferred by amino acid changes in the spike protein that include three substitutions (Y453F, I692V, and M1229I) and a loss of two amino acid residues 69 and 70 (ΔH69/V70), were evaluated in a virus microneutralization assay. Compared to a reference strain, the Cluster 5 variant showed reduced neutralization in a proportion of convalescent human COVID-19 samples. The findings underscore the need for active surveillance SARS-CoV-2 infection and virus evolution in susceptible animal hosts.
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影响因子: --
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