How does the hepatitis D Virus bypass the immune system?

What is this research project about?

Schematic figure of the hepatitis B and hepatitis D virus (Created with Biorender).

What is this research project about?

Infection with the hepatitis D virus (HDV) induces the least frequent but most severe form of chronic viral hepatitis, inducing liver cirrhosis and hepatocellular carcinoma in ~70% of patients. Development of chronic infection is thought to be immune-mediated, however there is not sufficient data available to support this. Chronic HDV infection results from either simultaneous infection with the hepatitis B virus (HBV) or superinfection of patients already infected with HBV. The aim of this project is to define how HDV circumvents the immune system leading to chronic infection.

What’s the current status?

With high rates of chronicity and the associated risk for the development of end stage liver disease and hepatocellular carcinoma, prevention of infection and/or effective antiviral treatment options are decisive. Currently, the only available antiviral treatment options are pegylated-interferon alpha with an efficacy of 25-33% and bulevirtide. The latter has only a conditional authorization in Europe, as long-term data on its efficacy are still missing. Understanding mechanisms of chronicity and disease pathogenesis are essential for the development of personalized treatment options, which are not available for chronic HDV infection so far.

Overview of the planned study (created with Biorender).

What are the project goals?

The aim of the project is to characterize and understand why the immune system leads to the establishment and maintenance of chronic HDV infection. These insights will provide the cornerstone for the development of personalized treatment options and prevention strategies in the future. Thereby, the project will alleviate the burden of disease associated with HDV infection in the long-term.

How do we get there?

Our preliminary work shows that immune cells, and especially CD4+ T cells, are implicated in viral control during chronic HDV infection. Thus, we would like to use a systems immunology approach to dissolve the host susceptibility to HDV infection, with a special focus on CD4+ T cells. Here, immune-cell subsets will be analyzed in different patient cohorts by flow cytometry, single-cell transcriptomics, epigenetics and proteomics. Interesting findings will be validated in vitro and in vivo with an ultimate goal to generate an immunological biomarker or treatment approach.

Projectleader

Project title: Dissolving immune control of hepatitis D virus infection

Publications of the Project B14

Publications of the Project B14