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

最近的研究表明，一些心脏病是由丙型肝炎病毒（HCV）感染引起的。在本研究中，我们对心肌炎、扩张型心肌病（DCM）和肥厚型心肌病（HCM）患者的心脏活检标本进行PCR分析，以检测病毒基因组。结果表明，HCV是这些疾病的病因之一。此外，我们研究了HLA分型与HCV相关DCM和HCM易感性的关系，发现HLA-DRB 1 ^*0201在HCV Ab阳性DCM中显著升高，HLA-DRB 1 ^*0901-和DQB 1 ^*0303在HCV Ab阳性HCM中显著升高。我们试图建立一种HCV心肌病的小鼠模型。鉴于小鼠对HCV不敏感，本研究构建了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。获得了两个过表达结构蛋白的小鼠品系和一个过表达非结构蛋白的小鼠品系。我们现在正在分析这些小鼠。自然发生的高变区变异体的出现可能会让病毒逃脱CTL的细胞毒性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决定HCV感染持续到心脏疾病的高变区的特定序列。

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.