Establishment of an African green monkey model for COVID-19 and protection against re-infection.
Establishment of an African green monkey model for COVID-19 and protection against re-infection.
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DOI：
10.1038/s41590-020-00835-8
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发表时间：
2021-01
影响因子：
30.5
通讯作者：
Cross RW
中科院分区：
文献类型：
--
作者：
Woolsey C;Borisevich V;Prasad AN;Agans KN;Deer DJ;Dobias NS;Heymann JC;Foster SL;Levine CB;Medina L;Melody K;Geisbert JB;Fenton KA;Geisbert TW;Cross RW
严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2）是导致COVID-19全球大流行的原因。研究COVID-19的发病机制以及筛选疫苗和治疗方法迫切需要动物模型。我们发现非洲绿色猴（AGM）支持SARS-CoV-2的强大复制，并发展出明显的呼吸道疾病，这可能比其他非人灵长类物种更准确地反映人类COVID-19病例。在包括直肠拭子在内的粘膜样本中检测到SARS-CoV-2，最晚在暴露后15天。血液和组织中明显的炎症和凝血障碍是突出的特征。转录组分析表明，刺激干扰素和白细胞介素6途径的支气管肺泡灌洗液样本和自然杀伤细胞和T细胞相关的转录抑制外周血。尽管初次攻毒后抗体滴度略有下降，但增强的抗体和细胞应答有助于在用相同菌株再次攻毒后快速清除。这些数据支持AGM在研究COVID-19发病机制和测试医疗对策方面的效用。感染SARS-CoV-2的非洲绿色猴重现了人类COVID-19的病理特征。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an unprecedented global pandemic of COVID-19. Animal models are urgently needed to study the pathogenesis of COVID-19 and to screen vaccines and treatments. We show African green monkeys (AGMs) support robust SARS-CoV-2 replication and develop pronounced respiratory disease, which may more accurately reflect human COVID-19 cases than other nonhuman primate species. SARS-CoV-2 was detected in mucosal samples, including rectal swabs, as late as 15 days post-exposure. Marked inflammation and coagulopathy in blood and tissues were prominent features. Transcriptome analysis demonstrated stimulation of interferon and interleukin 6 pathways in bronchoalveolar lavage samples and repression of natural killer cell- and T cell-associated transcripts in peripheral blood. Despite a slight waning in antibody titers after primary challenge, enhanced antibody and cellular responses contributed to rapid clearance after re-challenge with an identical strain. These data support the utility of AGM for studying COVID-19 pathogenesis and testing medical countermeasures. African Green monkeys infected with SARS-CoV-2 recapitulate pathological features of human COVID-19.
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