Simulation of COVID-19 symptoms in a genetically engineered mouse model: implications for the long haulers.
Simulation of COVID-19 symptoms in a genetically engineered mouse model: implications for the long haulers.
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DOI：
10.1007/s11010-022-04487-0
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发表时间：
2023-01
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
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作者：
由一种不断出现的病毒病原体（通常称为严重急性呼吸综合征冠状病毒 2 或 SARS-CoV-2）引发的持续大流行（也称为冠状病毒病 19；COVID-19）揭示了受感染人类的独特病理学发现以及尸检观察结果。疾病症状和尸检观察的清单太长，无法一一提及；然而，SARS-CoV-2 给“长途运输者”带来了一种全新的临床综合症，包括呼吸困难、胸痛、心动过速、脑雾、运动不耐受和极度疲劳。我们认为，有效治疗和预防策略的进一步改进将受益于经过验证的动物疾病模型。在此背景下，我们设计了一项研究，并证明基因工程小鼠表达人类血管紧张素转换酶2； ACE-2（SARS-CoV-2 病原体用于进入宿主细胞的受体）是模拟 COVID-19 重要临床特征的绝佳研究资源。当鼻内给予重组 SARS-CoV-2 刺突蛋白 (SP) 时，ACE-2 小鼠模型（对 SARS-CoV-2 敏感）表现出深刻的细胞因子风暴，能够改变生理参数，包括心脏功能的显着变化以及多器官损伤，这通过组织学发现得到进一步证实。更重要的是，尸检过程中发现，SP 治疗小鼠的内脏器官显示出血栓性血凝块。因此，ACE-2工程小鼠似乎是研究病毒发病机制的合适模型，从而为识别和表征适当的预防措施以及治疗方法铺平了道路，以用于COVID-19的管理。
The ongoing pandemic (also known as coronavirus disease-19; COVID-19) by a constantly emerging viral agent commonly referred as the severe acute respiratory syndrome corona virus 2 or SARS-CoV-2 has revealed unique pathological findings from infected human beings, and the postmortem observations. The list of disease symptoms, and postmortem observations is too long to mention; however, SARS-CoV-2 has brought with it a whole new clinical syndrome in “long haulers” including dyspnea, chest pain, tachycardia, brain fog, exercise intolerance, and extreme fatigue. We opine that further improvement in delivering effective treatment, and preventive strategies would be benefited from validated animal disease models. In this context, we designed a study, and show that a genetically engineered mouse expressing the human angiotensin converting enzyme 2; ACE-2 (the receptor used by SARS-CoV-2 agent to enter host cells) represents an excellent investigative resource in simulating important clinical features of the COVID-19. The ACE-2 mouse model (which is susceptible to SARS-CoV-2) when administered with a recombinant SARS-CoV-2 spike protein (SP) intranasally exhibited a profound cytokine storm capable of altering the physiological parameters including significant changes in cardiac function along with multi-organ damage that was further confirmed via histological findings. More importantly, visceral organs from SP treated mice revealed thrombotic blood clots as seen during postmortem examination. Thus, the ACE-2 engineered mouse appears to be a suitable model for studying intimate viral pathogenesis thus paving the way for identification, and characterization of appropriate prophylactics as well as therapeutics for COVID-19 management.
影响因子：
4.4
作者：
Morrison JC;Jia L;Cepurna W;Guo Y;Johnson E
通讯作者：
Johnson E