Subversion of immune responses by hepatitis C virus: immunomodulatory strategies beyond evasion?

Hepatitis C virus (HCV) is an important human pathogen that causes mild to severe liver disease worldwide. This positive-strand RNA virus is remarkably efficient at establishing persistent infection. In order for a non-cytopathic virus such as HCV to persist, the virus must escape immune recognition or inhibit the host immune responses. Immune escape via mutations in antigenic sites may occur under selective pressure during B-cell or T-cell responses to HCV infection, and may serve as a mechanism for the establishment HCV persistence. In addition to antigenic variation, HCV is able to subvert the host immune response by encoding specific viral gene product(s). An understanding of the mechanisms behind HCV persistence will provide a basis for the rational design of vaccines and novel therapeutic agents targeting human HCV infection.