In Vivo Functions of Hepatitis C Virus Core Protein: A Study in a Mouse Model Generated by Hydrodynamics-based DNA Injection of the Core-expressing DNA

Abstract

Hydrodynamics-based DNA injection method was employed to establish a mouse model expressing the hepatitis C virus (HCV) core or the luciferase protein in the liver. The model was used to investigate the in vivo function of HCV core. Our results showed that both HCV core and luciferase proteins were expressed transiently in mouse liver, lasting for about 7～21 days. In the animals injected with core DNA, significant levels of CD4+ and CD8+ T-cells were recruited to the liver and core-specific cytotoxic T-lymphocyte responses were detected in their spleens. The same DNA injection in immunodeficient non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, however, led to prolonged core gene expression, lasting for up to 56 days. Mice expressing the core protein were shown to be more resistant to Fas-mediated death than those without core protein. Our mouse experiments thus indicated that expression of HCV core in mouse liver does not exhibit immunosuppressive effects that can prevent the hepatocytes from immune clearance, but could protect them against Fas-mediated apoptotic death.