Hepatitis C virus--T-cell responses and viral escape mutations

Abstract

Hepatitis C virus (HCV) is a small, enveloped RNA virus and the number of HCV-infected individuals worldwide is estimated to be approximately 170 million. Most HCV infections persist, with up to 80% of all cases leading to chronic hepatitis associated with liver fibrosis, cirrhosis, and hepatocellular carcinoma. HCV-host interactions have a crucial role in viral survival, persistence, pathogenicity of infection, and disease progression. Maintenance of a vigorous, sustained cellular immune response recognizing multiple epitopes is essential for viral clearance. To escape immune surveillance, HCV alters its epitopes so that they are no-longer recognized by T cells and neutralizing antibodies, in addition to interfering with host cell cellular components and signaling pathways. The generation of escape variants is one of the most potent immune evasion strategies utilized by HCV. A large body of evidence suggests that single or multiple mutations within HLA-restricted epitopes contribute to viral immune escape and establishment of viral persistence. Further elucidation of the molecular mechanisms underlying immune escape will aid in the design of novel vaccines and therapeutics for the disease.