Phylogenomic characterization of endogenous and exogenous flaviviruses

The availability of genomic data provides a major asset in characterizing the evolutionary dynamics that underlie viral emergence and establishment in human populations. These factors are, however, still unknown for one of the most important causes of severe chronic liver disease, the Hepatitis C Virus. This gap in our knowledge can to a large extent be attributed to the lack of a known reservoir of the virus. First discovered in 1989, HCV remained the sole representative of the Hepacivirus genus for over two decades, but novel discoveries are now greatly expanding the host range and diversity of hepaciviruses. To unravel how current HCV diversity was generated and how hepaciviruses were transmitted to humans and domesticated mammals, we aim to screen a unique set of rodent and bat samples from both Africa and Asia and generate complete genome data from the positives using state-of-the-art procedures. In addition, we will develop novel codon substitution model approaches in a Bayesian phylogenetic framework for the analyses of relatively deep viral evolutionary time scales, and complement it with efficient computational inference machinery. Armed with these new tools and data, we will perform a comprehensive evolutionary analysis of hepacivirus evolution, focusing on its evolutionary time scale, the impact of recombination and molecular adaption associated with cross-species transmissions.