Ferrets are valuable models for SARS-CoV-2 research.

Ferrets are valuable models for SARS-CoV-2 research.
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雪貂是SARS-CoV-2研究的重要模型。

DOI:
10.1177/03009858211071012
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发表时间:
2022-07
影响因子:
2.4
通讯作者:
--
中科院分区:
农林科学2区
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由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的2019年冠状病毒病(新冠肺炎)导致了一场持续的大流行,导致全球数百万人死亡。人类感染可无症状或导致发热、乏力、干咳、呼吸困难和急性呼吸窘迫综合征,在严重情况下伴有多器官衰竭。新冠肺炎的发病机制尚不完全清楚,目前应用了各种使用不同物种的模型。雪貂可以感染SARS-CoV-2,并有效地将病毒传播给接触动物的动物。与仓鼠不同,雪貂通常表现出轻微的疾病和仅限于上呼吸道的病毒复制。大多数报告采用鼻腔接种途径,而气管内感染模型的特征不是很好。在这里,我们介绍了通过气管内接种SARS-CoV-2的幼年雪貂的临床、病毒学和病理学数据。感染动物无明显临床症状,感染后4d病毒RNA载量达高峰,出现轻、中度鼻炎和肺内皮炎/血管炎。病毒抗原仅在鼻腔的呼吸道上皮细胞中发现,表明该部位的细胞具有特殊的趋向性。病毒抗原与上皮损伤和炎症细胞的涌入有关,包括激活的中性粒细胞释放中性粒细胞胞外陷阱。鼻腔呼吸道粘膜的扫描电子显微镜显示纤毛丢失、脱落和上皮细胞破裂。对目前建立的水貂SARS-CoV-2感染模型与SARS-CoV-2的致病机制进行了比较分析,指出了两种动物作为人畜共患贝塔冠状病毒研究模型的优缺点。
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an ongoing pandemic with millions of deaths worldwide. Infection of humans can be asymptomatic or result in fever, fatigue, dry cough, dyspnea, and acute respiratory distress syndrome with multiorgan failure in severe cases. The pathogenesis of COVID-19 is not fully understood, and various models employing different species are currently applied. Ferrets can be infected with SARS-CoV-2 and efficiently transmit the virus to contact animals. In contrast to hamsters, ferrets usually show mild disease and viral replication restricted to the upper airways. Most reports have used the intranasal inoculation route, while the intratracheal infection model is not well characterized. Herein, we present clinical, virological, and pathological data from young ferrets intratracheally inoculated with SARS-CoV-2. Infected animals showed no significant clinical signs, and had transient infection with peak viral RNA loads at 4 days postinfection, mild to moderate rhinitis, and pulmonary endothelialitis/vasculitis. Viral antigen was exclusively found in the respiratory epithelium of the nasal cavity, indicating a particular tropism for cells in this location. Viral antigen was associated with epithelial damage and influx of inflammatory cells, including activated neutrophils releasing neutrophil extracellular traps. Scanning electron microscopy of the nasal respiratory mucosa revealed loss of cilia, shedding, and rupture of epithelial cells. The currently established ferret SARS-CoV-2 infection models are comparatively discussed with SARS-CoV-2 pathogenesis in mink, and the advantages and disadvantages of both species as research models for zoonotic betacoronaviruses are highlighted.
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发表时间: 2003-11-27
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