Effect of host immune pressure on the genetic diversity of hepatitis C virus

[Truncated abstract] It is estimated that 3% of the world’s population is infected with the hepatitis C virus (HCV). Of those who become infected, approximately 20-45% will spontaneously clear the infection while for the remainder of individuals, the virus will persist. Of those individuals who develop chronic HCV infection, the negative health outcomes are severe, with many individuals developing cirrhosis of the liver and hepatocellular carcinoma (HCC). Accordingly, HCV continues to be the leading indicator of liver transplantation in Western countries. Treatment for hepatitis C is available, but the current standard of care is only successful in clearing viral infection in approximately 50% of individuals. Recent use of direct acting antivirals (DAAs) are likely to be effective against the main circulating HCV genotype 1 strain, but treatment will not stop re-infection; a common phenomena amongst high-risk exposure individuals. Although there is currently no vaccine available to protect from HCV infection, the virus is likely to be amenable to a T-cell based vaccine. This is supported by data from several studies that have shown that a strong and broad CD8+ and CD4+ HCV-specific T-cell response that is maintained during and after the acute phase of HCV infection is associated with clearance of the virus. Understanding the key targets of a successful host immune response against HCV and the mechanisms that promote functional T-cell maintenance will be critical for vaccine design and future therapeutics. However, such studies must account for the extensive viral and host genetic diversity at the population level- one of the critical challenges in universal HCV vaccine design...