Hepatitis B virus is a DNA virus with no apparent cytotoxicity, but can cause persistent
infection. Despite the development of an effective vaccine, an estimated 2 billion
people worldwide have evidence of past or present HBV infection; 300 million people
are chronic HBV surface antigen carriers and are at high risk of developing hepatocellular
carcinoma and liver cirrhosis. 20-30% of the chronically infected patients will develop
complications associated with HBV infection, causing more than 700,000 deaths annually.
The persistence of HBV in patients is due to an inadequate host immune response with
an absent or weak HBV-specific cytotoxic T lymphocyte response. It is therefore proposed
that HBV controls or evades endogenous immune responses, whereas activation by exogenous
stimuli results in an effective antiviral signalling. Immune evasion occurs not only
through pattern recognition receptor signalling, but also through control of cytokine
and interferon responses.
Aim: The aim of this project is to determine HBsAg- and HBeAg-mediated immune evasion
of potential HBV-sensing pattern recognition receptors (TLR2, TLR3, RIG-I/MDA5, STING
and cytosolic DNA sensors). In this context, key host proteins interacting with HBsAg
or HBeAg will be identified and their contribution to immune evasion will be investigated.
The impact of HBsAg or HBeAg on cytokine- and interferon-mediated responses and viral
effects on regulatory inflammatory networks in the liver will also be investigated.
