HCV genetic variability: its implication for both viral translational efficiency and resistance to direct antivirals

Hepatitis C virus (HCV) infection is one of the main causes of liver transplantation, mainly due to its ability to generate a chronic infection that can lead to hepatocarcinoma. For those patients who do not resolve the acute infection and become chronically infected, there are indirect antiviral treatments which do not eradicate the virus in all treated patients. Over the years, direct-acting antivirals (DAAs) have been developed that target specific proteins of the virus. Most of these drugs target the viral serine protease (NS3), the phosphoprotein NS5A and the viral polymerase (NS5B). Concomitant with the development of these drugs, and taking into account the evolutionary speed of viruses whose genome is composed of RNA (such as HCV), mutations have been generated that confer resistance to these new antivirals. Furthermore, different genetic variants have also been reported at the level of the IRES (internal ribosome entry site) that could be implicated in greater viral translational efficiency. This project aims to: a) study mutations at the level of the genes coding for NS3, NS5A and NS5B, in search of new variants and variants already associated with resistance to DAAs; b) analyse the natural variants of the IRES and their effect at the translational level.