HDV infection is attracting increasing research interest. Moreover, recent years have seen renewed interest in hepatitis A virus (HAV) infection that never establishes chronicity, yet has a very protracted course of infection. The outcome of hepatitis virus infections, either acute self-limiting or persistent is a dynamic process that is governed by the complex interplay of multiple host and viral parameters. These include an insufficient antiviral immune response, the tolerogenic liver microenvironment and viral factors that depend on the individual infecting pathogen. So far, research mainly focussed on identifying single molecules or pathways or observing isolated biological events by using steady-state analyses. However, understanding the molecular mechanisms determining elimination versus persistence of virus infection requires an integrative approach that must account for the complex and dynamic interplay of the various immune cells involved in antiviral defence, the viral factors, the immune-privileged liver microenvironment and its alterations induced by viral infection and immune responses.
Thus, TRR179 will use a holistic approach to unravel the interplay and the dynamics of immunological and viral parameters that determine the outcome of hepatitis virus infection. It will characterise the decisive molecular mechanisms and key immune cell populations in this dynamic crosstalk that contribute either to the successful spontaneous or deliberate therapeutic elimination versus those that contribute to the development of persistence of hepatitis virus infections in preclinical model systems and in patients. The long-term goal of TRR179 is to develop therapeutic concepts to break hepatitis virus persistence. To reach this ambitious goal, we have assembled an interdisciplinary research consortium of renowned experts and have been able to integrate internationally recognized cutting-edge technologies at the forefront of cell culture systems, immune-competent mouse models and patient cohorts. This initiative thus provides the framework to address the salient questions in the field and to conduct studies at the molecular and cellular level, translate the results into relevant preclinical in vivo systems and validate the findings in hepatitis virus-infected individuals. While this research programme focuses on a distinct class of medically highly relevant viruses, the immunological and virological principles and mechanisms uncovered here will likely be applicable to persistent infections by other pathogens. In this respect, the research programme has a high innovation potential that reaches far beyond viral hepatitis.

HDV infection is attracting increasing research interest. Moreover, recent years have seen renewed interest in hepatitis A virus (HAV) infection that never establishes chronicity, yet has a very protracted course of infection. The outcome of hepatitis virus infections, either acute self-limiting or persistent is a dynamic process that is governed by the complex interplay of multiple host and viral parameters. These include an insufficient antiviral immune response, the tolerogenic liver microenvironment and viral factors that depend on the individual infecting pathogen. So far, research mainly focussed on identifying single molecules or pathways or observing isolated biological events by using steady-state analyses. However, understanding the molecular mechanisms determining elimination versus persistence of virus infection requires an integrative approach that must account for the complex and dynamic interplay of the various immune cells involved in antiviral defence, the viral factors, the immune-privileged liver microenvironment and its alterations induced by viral infection and immune responses.
Thus, TRR179 will use a holistic approach to unravel the interplay and the dynamics of immunological and viral parameters that determine the outcome of hepatitis virus infection. It will characterise the decisive molecular mechanisms and key immune cell populations in this dynamic crosstalk that contribute either to the successful spontaneous or deliberate therapeutic elimination versus those that contribute to the development of persistence of hepatitis virus infections in preclinical model systems and in patients. The long-term goal of TRR179 is to develop therapeutic concepts to break hepatitis virus persistence. To reach this ambitious goal, we have assembled an interdisciplinary research consortium of renowned experts and have been able to integrate internationally recognized cutting-edge technologies at the forefront of cell culture systems, immune-competent mouse models and patient cohorts. This initiative thus provides the framework to address the salient questions in the field and to conduct studies at the molecular and cellular level, translate the results into relevant preclinical in vivo systems and validate the findings in hepatitis virus-infected individuals. While this research programme focuses on a distinct class of medically highly relevant viruses, the immunological and virological principles and mechanisms uncovered here will likely be applicable to persistent infections by other pathogens. In this respect, the research programme has a high innovation potential that reaches far beyond viral hepatitis.