Published online Apr 7, 2014. doi: 10.3748/wjg.v20.i13.3418
Revised: September 28, 2013
Accepted: November 28, 2013
Published online: April 7, 2014
Hepatitis C virus (HCV) infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control. Liver damage and disease progression during HCV infection are driven by both viral and host factors. Specifically, adaptive immune response carries out an essential task in controlling non-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery. HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion. To impair HCV-specific T cell reactivity, HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro- and anti-apoptotic proteins. In this review, the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed.
Core tip: In the last few years, the knowledge about the role of adaptive immune response in hepatitis C pathogenesis has increased exponentially. This review summarizes our current understanding of the role of antigen-specific responses in hepatitis C virus (HCV) control and liver damage and discusses recent findings that identify costimulatory molecules modulation, apoptosis induction and chemokine regulation as major HCV mechanisms to evade immune control.