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从上呼吸道脱落的上皮细胞塞有利于金黄地鼠(Mesocricetus auratus)在实验感染 A.2 巴西 SARS-CoV-2 株时远端肺部损伤。

Detached epithelial cell plugs from the upper respiratory tract favour distal lung injury in Golden Syrian hamsters (Mesocricetus auratus) when experimentally infected with the A.2 Brazilian SARS-CoV-2 strain.

机构信息

Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Medicina Experimental e Saúde, Rio de Janeiro, RJ, Brasil.

Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Desenvolvimento Tecnológico em Virologia, Rio de Janeiro, RJ, Brasil.

出版信息

Mem Inst Oswaldo Cruz. 2024 Oct 21;119:e240100. doi: 10.1590/0074-02760240100. eCollection 2024.

Abstract

BACKGROUND

The Golden Syrian hamster (Mesocricetus auratus), Ferrets (Mustela putorius furo), and macaques have been described as useful laboratory animals naturally susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

OBJECTIVES

To study the mechanism of lung injury, we describe the histopathological features of SARS-CoV-2 infection in Golden Syrian hamsters inoculated intranasally with the A.2 Brazilian strain.

METHODS

Hamsters were intranasally inoculated with the A.2 variant and euthanised at 3-, 5-, 10- and 15-days post-inoculation. The physical examination and body weight were recorded daily. Neutralising antibodies and viral RNA load of the respiratory tract were assessed during necropsies.

FINDINGS

The coronavirus disease 2019 (COVID-19) model presented body weight loss, high levels of respiratory viral RNA load, severe segmentary pneumonitis, and bronchial fistula besides lymphatic trapping and infiltration, like the human SARS-COV-2 pathogenesis. The presence of subepithelial lymphoeosinophilic infiltrate was highlighted in our results; it contributed to the detachment of SARS-CoV-2 nucleocapsid-positive epithelial cells resulting in the infectious cell plugs.

MAIN CONCLUSIONS

The SARS-CoV-2 caused segmentary pneumonia and vascular damage. In our comprehension, the infectious cell plugs, as being aspirated from the upper respiratory tract into the terminal bronchial lumen, work as a "Trojan horse", thus contributing to the dissemination of the SARS-CoV-2 infection into specific regions of the deep lung parenchyma.

摘要

背景

金黄地鼠(Mesocricetus auratus)、雪貂(Mustela putorius furo)和猕猴已被描述为易感染严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的有用实验动物。

目的

为了研究肺损伤的机制,我们描述了金黄地鼠鼻腔接种 A.2 巴西株后 SARS-CoV-2 感染的组织病理学特征。

方法

金黄地鼠经鼻腔接种 A.2 变体,于接种后 3、5、10 和 15 天安乐死。每日记录体格检查和体重。解剖时评估呼吸道中和抗体和病毒 RNA 载量。

结果

COVID-19 模型表现为体重减轻、呼吸道病毒 RNA 载量高、严重节段性肺炎和支气管瘘,此外还有淋巴捕获和浸润,类似于人类 SARS-CoV-2 发病机制。我们的结果强调了黏膜下淋巴嗜酸性浸润的存在;它有助于 SARS-CoV-2 核衣壳阳性上皮细胞的脱落,导致感染细胞栓的形成。

主要结论

SARS-CoV-2 引起节段性肺炎和血管损伤。在我们的理解中,感染细胞栓作为从上呼吸道吸入到终末支气管腔的“特洛伊木马”,有助于 SARS-CoV-2 感染向深部肺实质的特定区域传播。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8688/11493349/ab87130a831e/1678-8060-mioc-119-e240100-gf1.jpg

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