Severe acute respiratory syndrome coronavirus infection of Golden Syrian hamsters
Severe acute respiratory syndrome coronavirus infection of Golden Syrian hamsters
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DOI：
10.1128/jvi.79.1.503-511.2005
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发表时间：
2005-01-01
影响因子：
5.4
通讯作者：
Subbarao, K
中科院分区：
文献类型：
--
作者：
Roberts, A;Vogel, L;Subbarao, K
为了评估针对严重急性呼吸综合征冠状病毒(SARS CoV)的候选疫苗和抗病毒药物的有效性，需要建立小动物模型。我们调查了SARS冠状病毒感染5周龄叙利亚金黄地鼠的能力。当给药时，SARS冠状病毒在肺部和鼻甲中复制到高滴度。下呼吸道复制高峰出现在感染后第2天(P.I.)在第7天被证明是清白的。免疫后第14天，少数金黄地鼠鼻甲中病毒水平较低。呼吸道上皮细胞中的病毒复制伴随着感染早期的细胞坏死，随后的炎症反应与病毒清除、肺组织灶性固结以及最终的肺组织修复相一致。尽管呼吸道病毒复制和相关病理水平很高，但仓鼠没有表现出疾病的证据。免疫后第7天血清中检测到中和抗体，免疫后第28天检测到中和抗体。已超过1：400。仓鼠在第28天感染SARS冠状病毒。在呼吸道内完全免受病毒复制和伴随的病理影响。将这些数据与小鼠模型进行比较，SARS CoV在仓鼠的呼吸道中复制到更高的滴度和更长的持续时间，并伴随着老鼠所没有的显著病理。在小鼠身上没有检测到SARS冠状病毒的病毒血症和肺外传播到肝和脾，这是在仓鼠身上看到的。因此，仓鼠作为评估抗病毒药物和针对SARS冠状病毒复制的候选疫苗的模型优于小鼠。
Small animal models are needed in order to evaluate the efficacy of candidate vaccines and antivirals directed against the severe acute respiratory syndrome coronavirus (SARS CoV). We investigated the ability of SARS CoV to infect 5-week-old Golden Syrian hamsters. When administered intranasally, SARS CoV replicates to high titers in the lungs and nasal turbinates. Peak replication in the lower respiratory tract was noted on day 2 postinfection (p.i.) and was cleared by day 7 p.i. Low levels of virus were present in the nasal turbinates of a few hamsters at 14 days p.i. Viral replication in epithelial cells of the respiratory tract was accompanied by cellular necrosis early in infection, followed by an inflammatory response coincident with viral clearance, focal consolidation in pulmonary tissue, and eventual pulmonary tissue repair. Despite high levels of virus replication and associated pathology in the respiratory tract, the hamsters showed no evidence of disease. Neutralizing antibodies were detected in sera at day 7 p.i., and mean titers at day 28 p.i. exceeded 1:400. Hamsters challenged with SARS CoV at day 28 p.i. were completely protected from virus replication and accompanying pathology in the respiratory tract. Comparing these data to the mouse model, SARS CoV replicates to a higher titer and for a longer duration in the respiratory tract of hamsters and is accompanied by significant pathology that is absent in mice. Viremia and extrapulmonary spread of SARS CoV to liver and spleen, which are seen in hamsters, were not detected in mice. The hamster, therefore, is superior to the mouse as a model for the evaluation of antiviral agents and candidate vaccines against SARS CoV replication.