Intranasal Infection of Ferrets with SARS-CoV-2 as a Model for Asymptomatic Human Infection.

Intranasal Infection of Ferrets with SARS-CoV-2 as a Model for Asymptomatic Human Infection.
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DOI:
10.3390/v13010113
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发表时间:
2021-01-15
期刊:
Viruses
影响因子:
--
通讯作者:
Brookes SM
Brookes SM
中科院分区:
其他
文献类型:
--
作者:
Everett HE;Lean FZX;Byrne AMP;van Diemen PM;Rhodes S;James J;Mollett B;Coward VJ;Skinner P;Warren CJ;Bewley KR;Watson S;Hurley S;Ryan KA;Hall Y;Simmons H;Núñez A;Carroll MW;Brown IH;Brookes SM

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雪貂通过实验接种了 SARS-CoV-2(严重急性呼吸综合征 (SARS) 相关冠状病毒 2),以评估感染动态和宿主反应。在由此产生的亚临床感染期间,在接种后 2 至 21 天 (dpi) 之间监测病毒 RNA,并在 4 至 6 dpi 之间在上呼吸道达到峰值。对三只动物样本中的病毒基因组序列分析鉴定出相对于接种物的 Y453F 核苷酸取代。在环境样本中也检测到了病毒 RNA,特别是在雪貂皮毛拭子中。显微镜分析显示上呼吸道组织中存在病毒蛋白和RNA,特别是鼻甲的呼吸道和嗅粘膜细胞,包括嗅觉神经元细胞。从 21 dpi 起检测到对刺突和核蛋白的抗体反应,但病毒中和活​​性较低。间隔 17 天后,对两只雪貂进行第二次鼻内接种(再次暴露)并没有重新启动病毒 RNA 脱落,但确实放大了一只动物的体液反应。因此,雪貂可以通过实验感染SARS-CoV-2来模拟人类无症状感染。
Ferrets were experimentally inoculated with SARS-CoV-2 (severe acute respiratory syndrome (SARS)-related coronavirus 2) to assess infection dynamics and host response. During the resulting subclinical infection, viral RNA was monitored between 2 and 21 days post-inoculation (dpi), and reached a peak in the upper respiratory cavity between 4 and 6 dpi. Viral genomic sequence analysis in samples from three animals identified the Y453F nucleotide substitution relative to the inoculum. Viral RNA was also detected in environmental samples, specifically in swabs of ferret fur. Microscopy analysis revealed viral protein and RNA in upper respiratory tract tissues, notably in cells of the respiratory and olfactory mucosae of the nasal turbinates, including olfactory neuronal cells. Antibody responses to the spike and nucleoprotein were detected from 21 dpi, but virus-neutralizing activity was low. A second intranasal inoculation (re-exposure) of two ferrets after a 17-day interval did not produce re-initiation of viral RNA shedding, but did amplify the humoral response in one animal. Therefore, ferrets can be experimentally infected with SARS-CoV-2 to model human asymptomatic infection.
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