The phylodynamics of hepatitis C virus in a clinical and public health context

Hepatitis C virus (HCV) is a blood-borne RNA virus that infects the liver of its human host. Worldwide an estimated 80 million people suffer from viraemic HCV infections resulting in more than half a million deaths annually. HCV is a rapidly evolving virus that can quickly adapt to environmental change. Consequently, genetic sequences that have been sampled over time can be used to infer the evolutionary dynamics of the virus. These dynamics, which shapes the phylogenetic patterns from population level to within a single host is more commonly known as phylodynamics. The focus of this thesis is on the phylodynamics of HCV within- and between-host placed in a clinical and public health context. The genetic variation of HCV has been mainly assessed with deep sequencing technologies and the dynamics of this variation with phylogenetic analysis. With this, we were able to characterize genetic diversity and the evolutionary dynamics of the within- and between-host HCV populations at an unprecedented depth. This thesis includes work that investigates the transmission of drug resistant associated viral variants among transmission networks of men who have sex with men. In addition, we explored the evolution of the HCV envelope genes in chronically infected patients, these genes play an important role in the host immune evasion. And we showed that multiple HCV infections are more common among people who inject drugs than previously reported using conventional sequencing technologies. These findings are relevant to clinical decision-making and public health strategies aimed to reduce the burden of HCV infections.