HCV susceptibility and host genetics

Hepatitis C Virus (HCV) infection still poses a major health problem worldwide. The prevalence varies across countries with an estimated ~1% from the total population being infected. Major advancements have been made over the last years in the development of therapeutics to treat HCV infection, which are typically well-tolerated oral direct-acting antiviral (DAA) therapies with cure rates reaching above 90%. DAAs provide a promising means of preventing HCV infection, but this is still at high cost and is unlikely to fully eradicate the virus. Therefore, efforts to develop an effective vaccine or HCV entry inhibitors against HCV are still warranted and highly desirable. This thesis focuses on HCV susceptibility, host genetics and viral host interactions that are associated with HCV infection and transmission. Susceptibility to HCV infection can be influenced by host genetic factors, but that this is not driven by a single allele. The impact of genetic factors will be potentially cumulative and being exposure route dependent. Therefore, it is of importance that future studies use well classified populations in genetic association studies. Several interesting targets have been identified for further functional studies in assessing their functional role in modulating HCV transmission. Overall, the findings in this thesis suggest that newly developed HCV transmission prevention strategies need to consider the biological processes involved with transmission and target them appropriately.