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

由于有共同的传播途径以及乙型肝炎病毒和丙型肝炎病毒在全球的高发病率，两种病毒的合并感染很常见。临床研究表明，HBV-HCV合并感染的过程不同于单一感染：HBV-HCV合并感染表现出更严重的临床过程，迅速和频繁地发展为肝硬化和肝细胞癌（HCC）。2. 共同感染导致病毒相互作用，相互抑制病毒。可能的机制是调节t细胞介导的免疫反应，适应性免疫反应在HBV和HCV的发病机制、临床病程和复制控制中起关键作用。此外，有效的t细胞应答是持续消除HBV和HCV的先决条件。因此，免疫调节过程对于病毒持久性的发展和治疗靶向至关重要。因此，本项目的目的是验证HBV-HCV合并感染是否比单感染影响t细胞介导的免疫反应。为此，将建立一种新的HBV-HCV共感染免疫细胞培养系统。此外，HBV- hcv合并感染对cccDNA的影响也将被研究，cccDNA是HBV持久性的重要储存库。将采用结构蛋白内携带突变的HBV构建物以及HepaRG细胞培养系统。

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.