Co-infection of respiratory bacterium with severe acute respiratory syndrome coronavirus induces an exacerbated pneumonia in mice
Co-infection of respiratory bacterium with severe acute respiratory syndrome coronavirus induces an exacerbated pneumonia in mice
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DOI：
10.1111/j.1348-0421.2008.00011.x
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发表时间：
2008-02-01
影响因子：
2.6
通讯作者：
Taguchi, Fumihiro
中科院分区：
文献类型：
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作者：
Ami, Yasushi;Nagata, Noriyo;Taguchi, Fumihiro
SARS-CoV在表达其受体的各种组织中生长，尽管在肺部和严重呼吸道疾病中高度复制的机制还不清楚。我们最近发现，弹性蛋白酶增强了培养细胞中的SARS-CoV感染，这表明SARS的发展可能是由于弹性蛋白酶介导的增强了肺部的SARS-CoV感染。为了探索这种可能性，我们检查了小鼠同时感染SARS-CoV和Pp（一种引起肺部产生弹性蛋白酶的低致病性细菌）是否会导致肺炎恶化。同时感染SARS-CoV和Pp的小鼠会出现严重的呼吸道疾病，并伴有大范围的体重减轻，导致33-90%的死亡率。肺炎加重的小鼠表现出肺部病毒感染增强，组织病理学病变与人类SARS病例相似。鼻内给药LPS，另一种弹性蛋白酶诱导剂，表现出类似于Pp感染的效果。因此，这项研究表明，小鼠肺炎加重是由SARS冠状病毒和呼吸道细菌共同感染引起的，这种细菌诱导肺部产生弹性蛋白酶，这表明弹性蛋白酶在肺炎加重中可能起作用。
SARS-CoV grows in a variety of tissues that express its receptor, although the mechanism for high replication in the lungs and severe respiratory illness is not well understood. We recently showed that elastase enhances SARS-CoV infection in cultured cells, which suggests that SARS development may be due to elastase-mediated, enhanced SARS-CoV infection in the lungs. To explore this possibility, we examined whether co-infection of mice with SARS-CoV and Pp, a low-pathogenic bacterium which elicits elastase production in the lungs, induces exacerbation of pneumonia. Mice co-infected with SARS-CoV and Pp developed severe respiratory disease with extensive weight loss, resulting in a 33-90% mortality rate. Mice with exacerbated pneumonia showed enhanced virus infection in the lungs and histopathological lesions similar to those found in human SARS cases. Intranasal administration of LPS, another elastase inducer, showed an effect similar to that of Pp infection. Thus, this study shows that exacerbated pneumonia in mice results from co-infection with SARS-CoV and a respiratory bacterium that induces elastase production in the lungs, suggesting a possible role for elastase in the exacerbation of pneumonia.