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动物模型与 SARS-CoV-2 诱导的肺部和神经系统损伤。

Animal models and SARS-CoV-2-induced pulmonary and neurological injuries.

机构信息

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

Fundação Oswaldo Cruz-Fiocruz, Instituto de Tecnologia em Imunobiológicos, Laboratório de Experimentação Animal, Rio de Janeiro, RJ, Brasil.

出版信息

Mem Inst Oswaldo Cruz. 2023 Jan 20;117:e220239. doi: 10.1590/0074-02760220239. eCollection 2023.

Abstract

Laboratory animals are essential mainly for experiments aiming to study pathogenesis and evaluate antivirals and vaccines against emerging human infectious diseases. Preclinical studies of coronavirus disease 19 (COVID-19) pathogenesis have used several animal species as models: transgenic human ACE2 mice (K18 mice), inbred BALB/c or C57BL/6N mice, ferrets, minks, domestic cats and dogs, hamsters, and macaques. However, the choice of an animal model relies on several limitations. Besides the host susceptibility, the researcher's experience with animal model management and the correct interpretation of clinical and laboratory records are crucial to succeed in preclinical translational research. Here, we summarise pathological and clinical findings correlated with virological data and immunological changes observed from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) experimental infections using different well-established SARS-CoV-2 animal model species. This essay aims to critically evaluate the current state of animal model translation to clinical data, as described in the human SARS-CoV-2 infection.

摘要

实验动物主要用于旨在研究发病机制和评估针对新发人类传染病的抗病毒药物和疫苗的实验。针对新型冠状病毒病 19(COVID-19)发病机制的临床前研究已经使用了几种动物物种作为模型:转人 ACE2 基因的小鼠(K18 小鼠)、近交 BALB/c 或 C57BL/6N 小鼠、雪貂、水貂、家猫和狗、仓鼠和猕猴。然而,动物模型的选择取决于几个限制因素。除了宿主易感性外,研究人员对动物模型管理的经验以及对临床和实验室记录的正确解释对于成功进行临床前转化研究至关重要。在这里,我们总结了与病毒学数据相关的病理和临床发现以及使用不同成熟的 SARS-CoV-2 动物模型观察到的免疫变化,这些动物模型被感染了严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)。本文旨在批判性地评估目前根据人类 SARS-CoV-2 感染情况将动物模型转化为临床数据的情况。

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