Establishment And Characterization Of A Chronic Viral Hepatitis Model Induced By Murine Hepatitis Virus Type 3

Objective:Viral hepatitis B and C are a worldwide disease with over 8% of HBV carrier and about 5% of HCV infection in China. The underline mechanism for the development of chronicity in HBV and HCV infection is not fully understood. Knowing the absent of an ideal representative model for chronic HBV and HCV infection, we dedicated to establish and characterize a substitute model of chronic viral hepatitis in C3H/HeJ mice induced by murine hepatitis viral type 3 (MHV-3). In order to understand the immune response in the development of chronicity in HBV and HCV infection, the change of T cell subsets were investigated in MHV-3 induced chronic hepatitis in C3H/HeJ mice.Methods:C3H/HeJ mice at the age of 6~-8weeks received 10pfu of purified MHV-3 intraperitoneally. We observed their general state of health and survival curves, and then evaluated the changes of liver histology (HE stain), serum biochemical indexes(ALT,AST,TP,ALB) and virus titer in liver tissue at 4, 6, 8, 9, 10, 12, 15, 20, 25, 30, 40 days post MHV-3 infection. The T cell subsets ratios of total T lymphocytes in blood and spleen were examined at 0,4,6,8,10,12 and 15 days post MHV-3 infection by flow cytometry.C3H/HeJ mice at the age of 6~-8weeks received 200ul normal saline were set up as control. Results:C3H/HeJ mice at the age of 6-8weeks received 10pfu of MHV-3 intraperitoneally and 63% of them developed a chronic course of virus infection characterized by persistence of lymphocyte infiltration and macrophage activation until 40 days post infection of the observed time. The mice underwent fluctuated serum ALT,AST levels and decreased TP,ALB level. The CD3~+CD4~-CD8~- (DN T cells) and CD3~+CD4~+CD25~+ T cell ratios in total T lymphocytes increased significantly.Conclusions:This substitute model could be applied in studies towards understanding the mechanism of chronic viral hepatitis. The significantly increased CD3~+CD4~-CD8~- and CD3~+CD4~+CD25~+T cell ratios in total T lymphocytes suggested that DN T and CD3~+CD4~+CD25~+T cells may play an important role in the process of the development of chronic viral hepatitis.