| Research Abstract |
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.
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