Pathology of experimental SARS coronavirus infection in cats and ferrets

Pathology of experimental SARS coronavirus infection in cats and ferrets
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DOI:
10.1354/vp.45-4-551
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发表时间:
2008-07-01
影响因子:
2.4
通讯作者:
Kuiken, T.
Kuiken, T.
中科院分区:
农林科学2区
文献类型:
--
作者:
Van den Brand, J. M. A.;Haagmans, B. L.;Kuiken, T.

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猫和雪貂中严重急性呼吸综合征冠状病毒 (SARS-CoV) 感染的病理学描述很少,而且 SARS-CoV 的受体血管紧张素转换酶 2 (ACE2) 在这些物种呼吸道中的分布也不清楚。我们观察了接种后 4 天 4 只猫和 4 只雪貂呼吸道中 SARS-CoV 抗原的表达和病变情况,以及 3 只猫和 3 只雪貂未感染时呼吸道中 ACE2 的表达。所有受感染的猫和雪貂均出现与 SARS-CoV 抗原表达相关的弥漫性肺泡损伤。猫的气管支气管腺炎是一种与 SARS-CoV 相关的新型病变。 SARS-CoV抗原表达主要发生在猫气管支气管粘膜下腺的I型和II型肺细胞和浆液细胞以及雪貂的II型肺细胞中。 ACE2表达主要发生在猫的I型和II型肺细胞、气管支气管杯状细胞、气管支气管粘膜下腺浆液性上皮细胞以及雪貂的II型肺细胞和气管支气管粘膜下腺浆液性上皮细胞中。总之,猫和雪貂感染 SARS-CoV 的病理学与人类相似,只是未观察到合胞体和透明膜。猫气管支气管腺炎的鉴定对 SARS 发病机制和 SARS-CoV 排泄具有潜在影响。最后,这些结果显示了 ACE2 表达对于体内 SARS-CoV 感染的重要性:虽然猫的 I 型和 II 型肺细胞中的 ACE2 表达与两种细胞类型中的 SARS-CoV 抗原表达相对应,但雪貂中 ACE2 和 SARS-CoV 抗原的表达主要限于 II 型肺细胞。
The pathology of severe acute respiratory syndrome-coronavirus (SARS-CoV) infection in cats and ferrets is poorly described, and the distribution of angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV, in the respiratory tracts of these species is unknown. We observed SARS-CoV antigen expression and lesions in the respiratory tracts of 4 cats and 4 ferrets at 4 days postinoculation and ACE2 expression in the respiratory tracts of 3 cats and 3 ferrets without infection. All infected cats and ferrets had diffuse alveolar damage associated with SARS-CoV antigen expression. A novel SARS-CoV-associated lesion was tracheo-bronchoadenitis in cats. SARS-CoV antigen expression occurred mainly in type I and II pneumocytes and serous cells of tracheo-bronchial submucosal glands of cats and in type II pneumocytes of ferrets. ACE2 expression occurred mainly in type I and II pneumocytes, tracheo-bronchial goblet cells, serous epithelial cells of tracheo-bronchial submucosal glands in cats, and type II pneumocytes and serous epithelial cells of tracheo-bronchial submucosal glands in ferrets. In conclusion, the pathology of SARS-CoV infection in cats and ferrets resembles that in humans except that syncytia and hyaline membranes were not observed. The identification of tracheo-bronchoadenitis in cats has potential implications for SARS pathogenesis and SARS-CoV excretion. Finally, these results show the importance of ACE2 expression for SARS-CoV infection in vivo: whereas ACE2 expression in type I and II pneumocytes in cats corresponded to SARS-CoV antigen expression in both cell types, expression of both ACE2 and SARS-CoV antigen in ferrets was limited mainly to type II pneumocytes.