Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus
Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus
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DOI：
10.1128/jvi.02012-06
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发表时间：
2007-01-01
影响因子：
5.4
通讯作者：
Perlman, Stanley
中科院分区：
文献类型：
--
作者：
McCray, Paul B., Jr.;Pewe, Lecia;Perlman, Stanley
由新型冠状病毒（SARS-CoV）引起的严重急性呼吸综合征（SARS）在2003年的流行期间导致了大量的发病率、死亡率和经济损失。虽然自2003年以来SARS冠状病毒感染没有在很大程度上复发，但它仍然是一个潜在的威胁。由于缺乏模仿人类疾病且可重复的动物模型，对SARS的理解和治疗方法的发展受到阻碍。在这里，我们表明，转基因小鼠表达SARS冠状病毒受体（人血管紧张素转换酶2 [hACE 2]）在气道和其他上皮细胞发展迅速致命的感染后，鼻内接种人株病毒。感染开始于气道上皮细胞，随后累及肺泡，肺外病毒扩散到大脑。感染导致肺中的巨噬细胞和淋巴细胞浸润以及肺和脑中的促炎细胞因子和趋化因子的上调。这种致死性感染SARS-CoV的模型对于研究发病机制和开发抗病毒治疗是有用的。
The severe acute respiratory syndrome (SARS), caused by a novel coronavirus (SARS-CoV), resulted in substantial morbidity, mortality, and economic losses during the 2003 epidemic. While SARS-CoV infection has not recurred to a significant extent since 2003, it still remains a potential threat. Understanding of SARS and development of therapeutic approaches have been hampered by the absence of an animal model that mimics the human disease and is reproducible. Here we show that transgenic mice that express the SARS-CoV receptor (human angiotensin-converting enzyme 2 [hACE2]) in airway and other epithelia develop a rapidly lethal infection after intranasal inoculation with a human strain of the virus. Infection begins in airway epithelia, with subsequent alveolar involvement and extrapulmonary virus spread to the brain. Infection results in macrophage and lymphocyte infiltration in the lungs and upregulation of proinflammatory cytokines and chemokines in both the lung and the brain. This model of lethal infection with SARS-CoV should be useful for studies of pathogenesis and for the development of antiviral therapies.