Participation of both host and virus factors in induction of severe acute respiratory syndrome (SARS) in F344 rats infected with SARS coronavirus
Participation of both host and virus factors in induction of severe acute respiratory syndrome (SARS) in F344 rats infected with SARS coronavirus
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DOI：
10.1128/jvi.01967-06
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发表时间：
2007-02-01
影响因子：
5.4
通讯作者：
Sata, Tetsutaro
中科院分区：
文献类型：
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作者：
Nagata, Noriyo;Iwata, Naoko;Sata, Tetsutaro
为了解严重急性呼吸综合征（SARS）相关冠状病毒（SARS-CoV）的发病机制，建立SARS-CoV动物模型，将法兰克福1株SARS-CoV在F344幼鼠体内连续传代。幼鼠对SARS-CoV敏感，但在鼻内接种后3至5天内迅速清除病毒。连续传代10代后，SARS-CoV在未出现临床症状的幼鼠呼吸道中的复制和毒力均增加。相比之下，感染传代病毒的成年大鼠表现出呼吸道症状和肺部严重的病理损伤。成年F344大鼠血清和肺组织中炎性细胞因子水平显著高于幼年大鼠。在SARS冠状病毒的体内传代过程中，在识别血管紧张素转换酶2（ACE 2）的病毒刺突蛋白（称为SARS冠状病毒受体）的结合域中引入了单个氨基酸取代。大鼠传代病毒更有效地感染CHO细胞表达大鼠ACE 2比原来的分离。这些结果有力地表明，宿主和病毒因素，如高龄和病毒适应是关键的SARS在大鼠中的发展。
To understand the pathogenesis and develop an animal model of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV), the Frankfurt 1 SARS-CoV isolate was passaged serially in young F344 rats. Young rats were susceptible to SARS-CoV but cleared the virus rapidly within 3 to 5 days of intranasal inoculation. After 10 serial passages, replication and virulence of SARS-CoV were increased in the respiratory tract of young rats without clinical signs. By contrast, adult rats infected with the passaged virus showed respiratory symptoms and severe pathological lesions in the lung. Levels of inflammatory cytokines in sera and lung tissues were significantly higher in adult F344 rats than in young rats. During in vivo passage of SARS-CoV, a single amino acid substitution was introduced within the binding domain of the viral spike protein recognizing angiotensin-converting enzyme 2 (ACE2), which is known as a SARS-CoV receptor. The rat-passaged virus more efficiently infected CHO cells expressing rat ACE2 than did the original isolate. These results strongly indicate that host and virus factors such as advanced age and virus adaptation are critical for the development of SARS in rats.