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Development of an animal model of cardiomyopathy by transfering hepatitis C virus genome.

通过转移丙型肝炎病毒基因组开发心肌病动物模型。

基本信息

批准号：
11557050
负责人：
MATSUMORI Akira
金额：
$ 8.19万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

Recent studies suggest that several heart disease are caused by hepatitis C virus (HCV) infection. In this project, we performed, PCR analysis of the hearts of biopsy specimen from patients with myocarditis, dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy (HCM) to detect the viral genomes. The results suggest that HCV is one of the cause of these diseases. Particularly, HCV genome was detected more frequently than enterovirus, which is considered to be a major cause of myocarditis.Furthermore, we investigated the relationship between HLA type and susceptibility to HCV-related DCM and HCM.HLA-DRB1^*0201 was significantly increased in HCV Ab positive DCM, and the HLA-DRB1^*0901- and DQB1^*0303 in HCV Ab positive HCM.Next, we tried to develop a murine model of HCV cardiomyopathy. Since it is known that mice are not susceptible to HCV, the expression plasmid of structural protein and non-structural protein driven by CMV promotor were constructed and transgenic mice were generated. Two lines of mice overexpressing structural protein and one line overexpressing non-structural protein were obtained. We are now analysing these mice.The emergence of naturally occurring hypervariable regions variants could let the virus escape from CTL the recognition by cytotoxic T lymphocytes and may be associated with HCV persistence. We are also analyzing w hether the specific sequence of hypervariable regions exists which determines persistence of HCV infection to heart diseases.

最近的研究表明，几种心脏病是由丙型肝炎病毒（HCV）感染引起的。在这个项目中，我们对心肌炎、扩张型心肌病（DCM）和肥厚型心肌病（HCM）患者的活检标本的心脏进行了PCR分析，以检测病毒基因组。结果提示丙型肝炎病毒是这些疾病的病因之一。特别是，HCV基因组比肠病毒更频繁地被检测到，这被认为是心肌炎的主要原因。此外，我们还研究了HLA类型与hcv相关的DCM和HCM易感性的关系。HCV Ab阳性DCM中HLA-DRB1^*0201显著升高，HCV Ab阳性HCM中HLA-DRB1^*0901-和DQB1^*0303显著升高。接下来，我们试图建立HCV心肌病的小鼠模型。由于已知小鼠对HCV不敏感，因此构建了CMV启动子驱动的结构蛋白和非结构蛋白表达质粒，制备了转基因小鼠。获得2株过表达结构蛋白的小鼠和1株过表达非结构蛋白的小鼠。我们现在正在分析这些老鼠。自然发生的高变区变异的出现可能使病毒从CTL中逃脱细胞毒性T淋巴细胞的识别，并可能与HCV的持久性有关。我们也在分析是否存在特定的高变区序列，这决定了HCV感染对心脏病的持久性。