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雪貂鼻腔感染 SARS-CoV-2 作为无症状人类感染的模型。

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

机构信息

Virology Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK.

Pathology and Animal Sciences Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK.

出版信息

Viruses. 2021 Jan 15;13(1):113. doi: 10.3390/v13010113.

DOI:10.3390/v13010113
PMID:33467732
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7830262/
Abstract

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.

摘要

雪貂被实验性地接种了 SARS-CoV-2(严重急性呼吸综合征(SARS)相关冠状病毒 2),以评估感染动力学和宿主反应。在随后的亚临床感染中,在接种后 2 至 21 天之间监测到病毒 RNA,并在 4 至 6 天达到上呼吸道腔的峰值。对来自 3 只动物的样本进行的病毒基因组序列分析发现,相对于接种物,存在 Y453F 核苷酸取代。病毒 RNA 也在环境样本中检测到,特别是在雪貂皮毛的拭子中。显微镜分析显示,在上呼吸道组织中存在病毒蛋白和 RNA,特别是在鼻甲的呼吸和嗅觉黏膜的细胞中,包括嗅觉神经元细胞。从 21 天开始检测到针对刺突蛋白和核蛋白的抗体反应,但病毒中和活性较低。在 17 天间隔后,对两只雪貂进行第二次鼻内接种(重新暴露),不会重新开始病毒 RNA 脱落,但会在一只动物中放大体液反应。因此,雪貂可以被实验性地感染 SARS-CoV-2,以模拟人类无症状感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f193/7830262/77df962db1b6/viruses-13-00113-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f193/7830262/6cfdafcb4f3c/viruses-13-00113-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f193/7830262/acc98ebb904e/viruses-13-00113-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f193/7830262/4fd5cc386bcf/viruses-13-00113-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f193/7830262/77df962db1b6/viruses-13-00113-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f193/7830262/6cfdafcb4f3c/viruses-13-00113-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f193/7830262/acc98ebb904e/viruses-13-00113-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f193/7830262/4fd5cc386bcf/viruses-13-00113-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f193/7830262/77df962db1b6/viruses-13-00113-g004.jpg

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