Cytotoxic T-lymphocyte responses to the hepatitis C virus in humans and chimpanzees

Hepatitis C virus is remarkably well-adapted for persistence in its human host. At least 60% of infected individuals develop a chronic viremia that is usually associated with significant long-term morbidity. Persistent virus replication in humans and experimentally infected chimpanzees occurs despite the presence of virus-specific, class I MHC-restricted cytotoxic T-lymphocyte activity in the peripheral blood and liver. The highly mutable RNA genome of HCV may be a key determinant in avoiding elimination by this immune response. It is hypothesized that immune selection pressure shifts the focus of the cytotoxic T-lymphocyte response from strong to weak epitopes, resulting in compromised clearance of the virus and chronic hepatocellular damage.