Periodic Reporting for period 3 - HBV1 (Innate immune responses to human hepatotropic viral infections)
Reporting period: 2018-06-01 to 2019-11-30
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.
This was supplemented by the use of human liver-chimeric mice, in which the normal mouse liver is repopulated with human hepatocytes, which renders the resulting ""humanized mouse"" highly susceptible to HBV, HCV as well as other highly human-tropic infectious diseases (e.g. Plasmodium spp., hepatitis E virus, hepatitis D virus). We were one of the few laboratories worldwide which integrated the use of human liver-chimeric and human immune system-containing mice in order to evaluate the role of the human interferon regulatory network in disease progression and viral control."