Immunology of hepatitis C virus infection.
Hepatitis C virus (HCV) is known for its ability to establish persistent infection and cause chronic hepatitis in most infected individuals. The pathogenesis of hepatic injury and the precise mechanisms underlying viral persistence are unknown. Accumulating evidence indicates that successful elimination of HCV is associated with the induction and maintaining of strong helper T-cell and cytotoxic T-cell responses against multiple viral epitopes. In contrast, patients who develop chronic HCV infection are characterized by the lack of strong viral-specific helper T-cell responses. The failure to mount and maintain strong HCV-specific T-cell responses may be determined by the genetics, especially the major histocompatibility complex background, of the host. However, it is likely that other host and viral factors are also involved in determining the outcome of HCV infection. Available data suggest that HCV is not cytopathic to hepatocytes and that liver injury associated with chronic HCV infection is likely to be mediated by immune responses against HCV-infected hepatocytes. In addition to hepatitis, HCV infection may also cause breaching of immune tolerance, leading to autoimmune disorders. Although the lack of a small animal model and a tissue culture system has impeded research on hepatitis C virus (HCV) infection, recent studies in humans and chimpanzees have significantly enhanced our understanding of the interaction between HCV and the host's immune system. This review focuses on the most recent advances in our understanding of the immunology of HCV infection. In particular, the possible mechanisms of how HCV establishes chronic infection are discussed. The pathogenesis of liver injury, the immunogenetics of HCV infection, and the effect of HCV infection on host's immune function are also reviewed.
Huang
L
L
Division of Gastroenterology, Brigham and Women's Hospital, Beth Israel Deaconess Hospital, Boston, Massachusetts 02115, USA.
Koziel
M J
MJ