Pathogenic and transcriptomic differences of emerging SARS-CoV-2 variants in the Syrian golden hamster model.
Pathogenic and transcriptomic differences of emerging SARS-CoV-2 variants in the Syrian golden hamster model.
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DOI：
10.1016/j.ebiom.2021.103675
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发表时间：
2021-11
期刊：
影响因子：
11.1
通讯作者：
Marzi A
中科院分区：
文献类型：
--
作者：
O'Donnell KL;Pinski AN;Clancy CS;Gourdine T;Shifflett K;Fletcher P;Messaoudi I;Marzi A
随着严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)的发现及其在全球的迅速传播，出现了新的病毒变种(VOC)。迫切需要了解新出现的变异体对宿主反应和疾病动态的影响，以促进疫苗和疗法的开发。叙利亚金黄仓鼠是重现2019年严重冠状病毒病关键方面的领先小动物模型(新冠肺炎)。我们用原始病毒(nCoV-WA1-2020)或首次在英国(B.1.1.7，阿尔法)和南非(B.1.351，贝塔)发现的VOC对仓鼠进行了SARS-CoV-2鼻腔接种，并分析了病毒载量和宿主反应。在感染所有三种变异体后，观察到相似的大体和组织病理学肺损害。尽管在受到挑战的动物的肺部和口腔拭子中发现了病毒基因组拷贝数的差异，但肺部的感染滴度在不同的变种之间是相似的。抗体中和能力不同，取决于原始攻击病毒和交叉变异的保护能力。对攻击后4天的肺样本的转录图谱(DPC)显示，在应对所有三种挑战时，显著诱导了抗病毒途径，在应对B.1.1.7感染时，具有更强烈的炎症特征。此外，在4DPC时没有检测到Spike蛋白的额外突变。虽然疾病严重程度和病毒脱落没有显著差异，但与原始病毒相比，新出现的VOC诱导了不同的体液反应和转录图谱。这些观察表明，VOC在急性早期反应或免疫调节方面的变化可能存在差异。美国国立卫生研究院NIAID校内研究计划；美国国立卫生研究院国家研究资源中心；美国国立卫生研究院国家翻译科学推进中心。
Following the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid spread throughout the world, new viral variants of concern (VOC) have emerged. There is a critical need to understand the impact of the emerging variants on host response and disease dynamics to facilitate the development of vaccines and therapeutics. Syrian golden hamsters are the leading small animal model that recapitulates key aspects of severe coronavirus disease 2019 (COVID-19). We performed intranasal inoculation of SARS-CoV-2 into hamsters with the ancestral virus (nCoV-WA1-2020) or VOC first identified in the United Kingdom (B.1.1.7, alpha) and South Africa (B.1.351, beta) and analyzed viral loads and host responses. Similar gross and histopathologic pulmonary lesions were observed after infection with all three variants. Although differences in viral genomic copy numbers were noted in the lungs and oral swabs of challenged animals, infectious titers in the lungs were comparable between the variants. Antibody neutralization capacities varied, dependent on the original challenge virus and cross-variant protective capacity. Transcriptional profiling of lung samples 4 days post-challenge (DPC) indicated significant induction of antiviral pathways in response to all three challenges with a more robust inflammatory signature in response to B.1.1.7 infection. Furthermore, no additional mutations in the spike protein were detected at 4 DPC. Although disease severity and viral shedding were not significantly different, the emerging VOC induced distinct humoral responses and transcriptional profiles compared to the ancestral virus. These observations suggest potential differences in acute early responses or alterations in immune modulation by VOC. Intramural Research Program, NIAID, NIH; National Center for Research Resources, NIH; National Center for Advancing Translational Sciences, NIH.
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