Animal Models of COVID-19 II. Comparative Immunology.
Animal Models of COVID-19 II. Comparative Immunology.
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DOI：
10.1093/ilar/ilab010
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发表时间：
2021-12-31
期刊：
影响因子：
2.5
通讯作者：
Zeiss CJ
中科院分区：
文献类型：
--
作者：
Veenhuis RT;Zeiss CJ
建立强有力的动物模型对于进一步了解免疫系统如何应对严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）感染至关重要。SARS-CoV-2的传播速度令人震惊，2019年严重冠状病毒病（COVID-19）的高死亡率要求基础科学和临床研究以前所未有的速度发展。先前开发的用于研究针对SARS-CoV的免疫反应的模型已经迅速部署到现在研究SARS-CoV-2。到目前为止，无论是小型动物模型还是大型动物模型，在感染SARS-CoV-2时都非常一致;然而，某些模型在回答特定的免疫学问题时比其他模型更有用。小动物模型，如叙利亚仓鼠、雪貂和携带hACE 2转基因的小鼠，似乎可靠地重现了COVID-19中观察到的初始细胞因子激增，并在感染早期显示出显著的先天性和适应性细胞浸润到肺部。此外，这些模型对病毒产生了强烈的抗体反应，可以防止再感染，并且存在可用于询问特定免疫学问题的遗传修饰版本。大型动物模型，如恒河猴和食蟹猴以及非洲绿色猴，对于了解免疫系统如何对SARS-CoV-2感染做出反应至关重要，因为它们被认为与人类最相似。这些模型被认为是评估疫苗效力和保护的金标准，并概括了初始细胞因子激增、免疫细胞浸润到肺中、血栓形成的某些方面以及抗体和T细胞对病毒的反应。在这篇综述中，我们讨论了先前用于SARS-CoV-2研究的小型和大型动物模型研究，这些研究可能有助于阐明COVID-19对标志性综合征的免疫学贡献。
Developing strong animal models is essential for furthering our understanding of how the immune system functions in response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. The alarming speed at which SARS-CoV-2 has spread, and the high mortality rate of severe Coronavirus Disease 2019 (COVID-19), has required both basic science and clinical research to move at an unprecedented pace. Models previously developed to study the immune response against SARS-CoV have been rapidly deployed to now study SARS-CoV-2. To date, both small and large animal models are remarkably consistent when infected with SARS-CoV-2; however, certain models have proven more useful when answering specific immunological questions than others. Small animal models, such as Syrian hamsters, ferrets, and mice carrying the hACE2 transgene, appear to reliably recapitulate the initial cytokine surge seen in COVID-19 as well as show significant innate and adaptive cell infiltration in to the lung early in infection. Additionally, these models develop strong antibody responses to the virus, are protected from reinfection, and genetically modified versions exist that can be used to ask specific immunological questions. Large animal models such as rhesus and cynomologus macaques and African green monkeys are critical to understanding how the immune system responds to SARS-CoV-2 infection because they are considered to be the most similar to humans. These models are considered the gold standard for assessing vaccine efficacy and protection, and recapitulate the initial cytokine surge, immune cell infiltration into the lung, certain aspects of thrombosis, and the antibody and T-cell response to the virus. In this review, we discuss both small and large animal model studies previously used in SARS-CoV-2 research that may be useful in elucidating the immunological contributions to hallmark syndromes observed with COVID-19.
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