Viral hepatitis including hepatitis B and C virus (HBV, HCV) are a major public health concern. Even though novel direct-acting antiviral drugs are currently facilitating the cure of HCV, HBV remains incurable. With over 257 million chronically infected patients living with chronic HBV, novel therapeutic interventions and curative approaches are urgently needed. Among the main reasons complicating the development of novel drugs is the very narrow species tropism of these viruses, which currently restrict work with hepatitis B virus in vitro and in vivo. Since both, HBV and HCV infect human hepatocytes, the main cell population within the liver, the study of these pathogens is furthermore complicated by the fragile nature of these cells. Cultures of human liver cells cannot be maintained for more than a few days and small-animal models for either virus are currently unavailable.
During the project we, and others, have described that innate immunity, predominantly through cell-intrinsic innate immune responses and interferon-stimulated effector genes are able to epigenetically suppress a number of human-tropic pathogens, including Epstein-Barr virus, hepatitis B virus and HIV. Interferons, which are the main molecular effector molecules for the induction of a potent innate immune response, resulting in the expression of several hundred interferon-stimulated genes (ISG), of which only a few have been characterized in detail.
The aim of this project was the development of novel pre-clinical platforms to study human-tropic hepatitis viruses which was achieved. The project also aimed to analyze host responses to hepatitis B and C virus on a single cell level on which progress was being made and a special emphasis of this research programme was the identification of novel targets for therapy to treat and eventually cure HBV infection. The Principal Investigator sadly passed away during the planned project period and the work curtailed so these aims were not completed.
