Exploring viral evolution with respect to disease progression and therapy-response in HCV infection.

Chronic hepatitis caused by the hepatitis C virus is a serious public health problem and affects more than 170 million people worldwide. Infection by HCV is defined by a complex interplay between virus and host. Already from the beginning, both virus and host genetics define the disease progression in a patient, ranging from spontaneous clearance to chronic infection potentially leading to liver cancer. Treatment options are limited, but viral clearance can be achieved in a large number of patients, depending on both viral and host characteristics. However, the emergence of resistant viral variants under drug selective pressure severely hampers therapeutic success. The population of closely related viruses in the patient, also known as quasispecies, evolves in response to immune and drug selective pressure. In this project we aim to develop the necessary in vitro and in silico tools to study within-host evolution and explore its relationship with disease progression and therapy response. Furthermore, we will study the emergence of drug resistance mutations under drug selective pressure. These results can be readily implemented in the management of HCV infected patients, giving clinicians an additional tool for individual patient guidance and treatment.

Keywords:Virus evolution, Hepatitis C virus, evolution, antiviral treatment, drug resistance

Disciplines:Scientific computing, Bioinformatics and computational biology, Public health care, Public health services, Microbiology, Systems biology, Laboratory medicine, Immunology