Important roles of HBe and HBs antigens in the evasion of endogenous innate immune responses in Hepatitis B Virus infection

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.

Publication History

Article published online:
20 January 2025