关键词: ACE2 CTSL SARS-CoV-2 TMPRSS2 air–liquid interface animals primary cell cultures respiratory tract tissue explants zoonosis

Mesh : Angiotensin-Converting Enzyme 2 Animals Animals, Wild COVID-19 Dogs Ferrets Humans Primary Cell Culture SARS-CoV-2 Spike Glycoprotein, Coronavirus

来  源:   DOI:10.3390/v14040828

Abstract:
Several animal species are susceptible to SARS-CoV-2 infection, as documented by case reports and serological and in vivo infection studies. However, the susceptibility of many animal species remains unknown. Furthermore, the expression patterns of SARS-CoV-2 entry factors, such as the receptor angiotensin-converting enzyme 2 (ACE2), as well as transmembrane protease serine subtype 2 (TMPRSS2) and cathepsin L (CTSL), cellular proteases involved in SARS-CoV-2 spike protein activation, are largely unexplored in most species. Here, we generated primary cell cultures from the respiratory tract of domestic and wildlife animals to assess their susceptibility to SARS-CoV-2 infection. Additionally, the presence of ACE2, TMPRSS2 and CTSL within respiratory tract compartments was investigated in a range of animals, some with unknown susceptibility to SARS-CoV-2. Productive viral replication was observed in the nasal mucosa explants and precision-cut lung slices from dogs and hamsters, whereas culture models from ferrets and multiple ungulate species were non-permissive to infection. Overall, whereas TMPRSS2 and CTSL were equally expressed in the respiratory tract, the expression levels of ACE2 were more variable, suggesting that a restricted availability of ACE2 may contribute to reduced susceptibility. Summarized, the experimental infection of primary respiratory tract cell cultures, as well as an analysis of entry-factor distribution, enable screening for SARS-CoV-2 animal reservoirs.
摘要:
几种动物容易感染SARS-CoV-2,如病例报告和血清学和体内感染研究所记录。然而,许多动物物种的易感性仍然未知。此外,SARS-CoV-2进入因子的表达模式,如受体血管紧张素转换酶2(ACE2),以及跨膜蛋白酶丝氨酸亚型2(TMPRSS2)和组织蛋白酶L(CTSL),参与SARS-CoV-2刺突蛋白激活的细胞蛋白酶,在大多数物种中大部分未被开发。这里,我们从家畜和野生动物的呼吸道产生原代细胞培养物,以评估它们对SARS-CoV-2感染的易感性.此外,在一系列动物中研究了呼吸道隔室中ACE2,TMPRSS2和CTSL的存在,一些对SARS-CoV-2的易感性未知。在狗和仓鼠的鼻粘膜外植体和精确切割的肺切片中观察到生产性病毒复制,而雪貂和多种有蹄类动物的培养模型不允许感染。总的来说,而TMPRSS2和CTSL在呼吸道中表达相等,ACE2的表达水平变化更大,提示ACE2的可获得性受限可能有助于降低易感性.总结,原发性呼吸道细胞培养物的实验性感染,以及对进入因素分布的分析,能够筛查SARS-CoV-2动物库。
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