Hepatitis C virus core and envelope proteins do not suppress the host's ability to clear a hepatic viral infection

Several hepatitis C virus (HCV) proteins have been shown in vitro to intera ct with host cellular components that are involved in immune regulation. Ho wever, there is a paucity of data supporting the relevance of these observa tions to the in vivo situation. To test the hypothesis that such an interac tion suppresses immune responses, we studied a line of transgenic C57BL/6 m ice that express the HCV core and envelope proteins in the liver. The poten tial effects of these proteins on the hepatic immune response were evaluate d by challenging these mice with a hepatotropic adenovirus. Both transgenic and nontransgenic mice developed similar courses of infection and cleared the virus from the liver by 28 days postinfection. Both groups of mice moun ted similar immunoglobulin G (IgG), IgG2a, interleukin-2, and tumor necrosi s factor alpha responses against the virus. Additionally, BALB/c mice were able to clear infection with recombinant adenovirus that does or does not e xpress the HCV core and envelope I proteins in the same manner. These data suggest that HCV core and envelope proteins do not inhibit the hepatic anti viral mechanisms in these murine experimental systems and thus favor a mode l in which HCV circumvents host responses through a mechanism that does not involve general suppression of intrahepatic immune responses.