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Replication and gene expression of SARS coronavirus and other animal coronaviruses

SARS冠状病毒和其他动物冠状病毒的复制和基因表达

基本信息

批准号：
16017308
负责人：
TAGUCHI Fumihiro
金额：
$ 9.6万
依托单位：
National Institute of Infectious Diseases
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

1) Research on SARS coronavirus (SARS-CoV) infection :It was reported that SARS-CoV enters into cells via endosomal pathway. We found that SARS-CoV also enters cells directly from cell surface, when cell-attached viruses are treated with proteases, such as trypsin or elastase that induces. S protein cleavage as well as fusion activity. Virus entry from plasma membrane was revealed to result in a 100 to 1000 more efficient infection than the infection via endosomal pathway. This could suggest that high replication of SARS-CoV in the lung or intestine, the major target organs of SARS, is attributed to the proteases produced in those organs. This protease-mediated enhancement of SARS-CoV infection could explain how severe respiratory disease is produced by SARS-CoV infection, even if this virus is allowed to grow in a variety of organs that express its receptor ACE2. Studies are in progress whether such proteases produced in mice induce severe respiratory disease or not.2) Research on murine coronavirus mouse hepatitis virus (MHV) infection :Highly neurotropic MHV, JIEVIV, spreads from cells infected via its receptor (CEACAM1) to CEACAM1-negative BHK cells (called receptor-independent infection). We have shown that JHMV virion can directly infect BHK by spinoculation (virus inoculated cells as well as inoculated viruses were spun at 3000 rpm for 2 h), indicating that JHMV virion has a unique feature for infection. It was further shown that this feature is dependent upon its S protein, which is activated for fusion by a naturally occurring manner, without binding to its specific receptor.

1)SARS冠状病毒（SARS-CoV）感染的研究：报道了SARS-CoV通过内体途径进入细胞。我们发现SARS-CoV也可以直接从细胞表面进入细胞，当细胞附着病毒用蛋白酶处理时，如胰蛋白酶或弹性蛋白酶诱导。S蛋白切割以及融合活性。发现病毒从质膜进入导致比通过内体途径的感染高100至1000的感染效率。这可能表明，SARS冠状病毒在肺或肠（SARS的主要靶器官）中的高复制归因于这些器官中产生的蛋白酶。这种蛋白酶介导的SARS-CoV感染增强可以解释SARS-CoV感染如何产生严重的呼吸道疾病，即使这种病毒被允许在表达其受体ACE 2的各种器官中生长。2）鼠冠状病毒小鼠肝炎病毒（MHV）感染的研究：高度嗜神经性的MHV（JIEVIV）通过其受体（CEACAM 1）从感染的细胞传播到CEACAM 1阴性的BHK细胞（称为受体非依赖性感染）。我们已经表明，JHMV病毒粒子可以直接感染BHK通过spinoculation（病毒接种的细胞以及接种的病毒在3000 rpm下旋转2小时），表明JHMV病毒粒子具有独特的感染特征。进一步表明，该特征取决于其S蛋白，S蛋白通过天然存在的方式被激活融合，而不结合其特异性受体。