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实验性 SARS-CoV-2 感染家猫后的免疫反应和发病机制。

Immune Responses and Pathogenesis following Experimental SARS-CoV-2 Infection in Domestic Cats.

机构信息

Wageningen Bioveterinary Research, Wageningen University & Research, 8221 RA Lelystad, The Netherlands.

Division of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.

出版信息

Viruses. 2023 Apr 25;15(5):1052. doi: 10.3390/v15051052.

DOI:10.3390/v15051052
PMID:37243138
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10222871/
Abstract

Several reports demonstrated the susceptibility of domestic cats to SARS-CoV-2 infection. Here, we describe a thorough investigation of the immune responses in cats after experimental SARS-CoV-2 inoculation, along with the characterization of infection kinetics and pathological lesions. Specific pathogen-free domestic cats ( = 12) were intranasally inoculated with SARS-CoV-2 and subsequently sacrificed on DPI (days post-inoculation) 2, 4, 7 and 14. None of the infected cats developed clinical signs. Only mild histopathologic lung changes associated with virus antigen expression were observed mainly on DPI 4 and 7. Viral RNA was present until DPI 7, predominantly in nasal and throat swabs. The infectious virus could be isolated from the nose, trachea and lungs until DPI 7. In the swab samples, no biologically relevant SARS-CoV-2 mutations were observed over time. From DPI 7 onwards, all cats developed a humoral immune response. The cellular immune responses were limited to DPI 7. Cats showed an increase in CD8+ cells, and the subsequent RNA sequence analysis of CD4+ and CD8+ subsets revealed a prominent upregulation of antiviral and inflammatory genes on DPI 2. In conclusion, infected domestic cats developed a strong antiviral response and cleared the virus within the first week after infection without overt clinical signs and relevant virus mutations.

摘要

已有多项报告表明,家猫易感染 SARS-CoV-2。在此,我们详细研究了感染 SARS-CoV-2 的实验猫的免疫反应,并对感染动力学和病理损伤进行了特征描述。将 12 只无特定病原体的家猫经鼻腔接种 SARS-CoV-2,随后于感染后第 2、4、7 和 14 天处死。所有感染猫均未出现临床症状。仅在感染后第 4 和 7 天观察到轻微的与病毒抗原表达相关的组织病理学肺部变化。病毒 RNA 持续存在至感染后第 7 天,主要存在于鼻拭子和咽拭子中。在感染后第 7 天之前,鼻、气管和肺中均可分离到有感染性的病毒。在拭子样本中,未随时间推移观察到具有生物学意义的 SARS-CoV-2 突变。自感染后第 7 天起,所有猫均产生了体液免疫反应。细胞免疫反应仅持续至感染后第 7 天。猫的 CD8+细胞数量增加,随后对 CD4+和 CD8+亚群的 RNA 序列分析表明,在感染后第 2 天,抗病毒和炎症基因的表达显著上调。综上,感染 SARS-CoV-2 的家猫产生了强烈的抗病毒反应,并在感染后第一周内清除了病毒,无明显临床症状和相关病毒突变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aed/10222871/5a936f38108a/viruses-15-01052-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aed/10222871/064154be398a/viruses-15-01052-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aed/10222871/321194a76978/viruses-15-01052-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aed/10222871/a80bd3fa9040/viruses-15-01052-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aed/10222871/9b4066d63707/viruses-15-01052-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aed/10222871/5a936f38108a/viruses-15-01052-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aed/10222871/064154be398a/viruses-15-01052-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aed/10222871/321194a76978/viruses-15-01052-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aed/10222871/a80bd3fa9040/viruses-15-01052-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aed/10222871/9b4066d63707/viruses-15-01052-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aed/10222871/5a936f38108a/viruses-15-01052-g003.jpg

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