Modeling SARS-CoV-2: Comparative Pathology in Rhesus Macaque and Golden Syrian Hamster Models.

Modeling SARS-CoV-2: Comparative Pathology in Rhesus Macaque and Golden Syrian Hamster Models.
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DOI:
10.1177/01926233211072767
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发表时间:
2022-04
影响因子:
1.5
通讯作者:
García-Sastre A
García-Sastre A
中科院分区:
医学4区
文献类型:
--
作者:
Choudhary S;Kanevsky I;Yildiz S;Sellers RS;Swanson KA;Franks T;Rathnasinghe R;Munoz-Moreno R;Jangra S;Gonzalez O;Meade P;Coskran T;Qian J;Lanz TA;Johnson JG;Tierney CA;Smith JD;Tompkins K;Illenberger A;Corts P;Ciolino T;Dormitzer PR;Dick EJ Jr;Shivanna V;Hall-Ursone S;Cole J;Kaushal D;Fontenot JA;Martinez-Romero C;McMahon M;Krammer F;Schotsaert M;García-Sastre A

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人类冠状病毒病2019(新冠肺炎)有多种表现,从无症状或轻微症状到严重疾病。合适的动物模型可以模拟不同程度的临床疾病表现,可以加快新冠肺炎疗法和疫苗的开发。在这里,我们证明了严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染导致了轻度肺炎猕猴的亚临床疾病和严重肺炎的叙利亚仓鼠的临床疾病。通过福尔马林固定、石蜡包埋(FFPE)聚合酶链式反应(PCR)、免疫组织化学或原位杂交证实SARS-CoV-2感染。用原位杂交或病毒空斑形成试验鉴定肺内复制病毒。据报道,在一些新冠肺炎患者中发现了病毒性脑炎,在一只猕猴中发现了病毒性脑炎,并通过免疫组织化学进行了确认。没有证据表明仓鼠患有脑炎。与猕猴相比,仓鼠的肺部炎症程度和分布要严重得多,并表现出血管变化和病毒诱导的细胞病变,如新冠肺炎患者中所见。仓鼠和猕猴的模型都没有证明有多系统炎症综合症的证据。这里提供的数据表明,猕猴可能适合于轻度无症状新冠肺炎肺炎和新冠肺炎相关性脑炎的机制研究,而叙利亚仓鼠可能更适合研究重度新冠肺炎肺炎。
Coronavirus disease 2019 (COVID-19) in humans has a wide range of presentations, ranging from asymptomatic or mild symptoms to severe illness. Suitable animal models mimicking varying degrees of clinical disease manifestations could expedite development of therapeutics and vaccines for COVID-19. Here we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulted in subclinical disease in rhesus macaques with mild pneumonia and clinical disease in Syrian hamsters with severe pneumonia. SARS-CoV-2 infection was confirmed by formalin-fixed, paraffin-embedded (FFPE) polymerase chain reaction (PCR), immunohistochemistry, or in situ hybridization. Replicating virus in the lungs was identified using in situ hybridization or virus plaque forming assays. Viral encephalitis, reported in some COVID-19 patients, was identified in one macaque and was confirmed with immunohistochemistry. There was no evidence of encephalitis in hamsters. Severity and distribution of lung inflammation were substantially more in hamsters compared with macaques and exhibited vascular changes and virus-induced cytopathic changes as seen in COVID-19 patients. Neither the hamster nor macaque models demonstrated evidence for multisystemic inflammatory syndrome (MIS). Data presented here demonstrate that macaques may be appropriate for mechanistic studies of mild asymptomatic COVID-19 pneumonia and COVID-19-associated encephalitis, whereas Syrian hamsters may be more suited to study severe COVID-19 pneumonia.
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