Impact of HBV-HCV coinfection on virus-specific cytotoxic T-cell responses and viral persistence

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Due to shared routes of transmission and due to high global incidences of HBV and HCV, coinfections with both viruses are common. Clinical studies have demonstrated that the course of HBV-HCV coinfection differs from monoinfections: 1. HBV-HCV coinfection shows a more severe clinical course with rapid and frequent development of liver cirrhosis and hepatocellular carcinoma (HCC). 2. Coinfection leads to viral interaction in terms of a reciprocal viral suppression. A possible mechanism is the modulation of the T-cell mediated immune response, as the adaptive immune response plays a key role for the pathogenesis, the clinical course, and the control of replication of HBV and HCV. Furthermore, an efficient T-cell response is a prerequisite for a sustained elimination of HBV and HCV. As a consequence, immunmodulatory processes are of utmost importance for the development and therapeutic targeting of viral persistence. Therefore, the aim of this project is to validate whether HBV-HCV coinfection influences the T-cell mediated immune response in comparison to monoinfection. For this purpose a novel immunological cell culture system of HBV-HCV coinfection will be established. In addition, the impact of HBV-HCV coinfection on cccDNA, an important reservoir of HBV persistence will be studied. HBV constructs harboring mutations within the structural proteins as well as the HepaRG cell culture system will be employed.