Major histocompatibility complex class-I presentation impaired in transgenic mice expressing hepatitis C virus...

Hepatitis C virus (HCV) infection is often persistent, but its mechanism and pathogenesis remain unclear. One mechanism through which HCV escapes systemic immunosurveillance might be via impaired dendritic cells (DCs), which are the most potent type of antigen-presenting cells. We examined whether HCV causes immunosuppression in DCs during maturation. We isolated immature DCs from the bone marrow of two founder lineages of transgenic mice harboring HCV cDNA expressing HCV structural proteins (nucleotides 294-3435), and studied how DC function is modified by HCV expression. Our data showed that the capacity of DCs expressing HCV structural proteins to stimulate T-cells was significantly impaired. Moreover, the surface expression of major histocompatibility complex (MHC) class-I molecules was significantly impaired on infected DC, especially with respect to H-2D. The transportation of H-2D to the cell surface during DC maturation was inhibited by HCV expression. However, the total amount of H-2D molecules produced by DC expressing HCV was not impaired. These results indicated that the immune response of DC infected with HCV is diminished and might be associated with the mechanism of persistent HCV infection.