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

HBV-HCV 共感染对病毒特异性细胞毒性 T 细胞反应和病毒持久性的影响

• 批准号: 134164077
• 负责人: Dr. Volker Brass
• 金额: --
• 依托单位: Division of Gastroenterology and Hepatology
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/134164077?language=en
• 关键词: Impact; HBV; HCV; coinfection; virus

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.

由于 HBV 和 HCV 具有共同的传播途径，且全球发病率较高，这两种病毒的双重感染很常见。临床研究表明，HBV-HCV 合并感染的病程与单一感染不同： 1. HBV-HCV 合并感染的临床病程更为严重，肝硬化和肝细胞癌 (HCC) 的发展迅速且频繁。 2. 混合感染导致病毒相互作用，即相互抑制病毒。一个可能的机制是 T 细胞介导的免疫反应的调节，因为适应性免疫反应在 HBV 和 HCV 的发病机制、临床过程以及复制控制中发挥着关键作用。此外，有效的 T 细胞反应是持续消除 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，该项目的目的是验证与单一感染相比，HBV-HCV 合并感染是否会影响 T 细胞介导的免疫反应。为此，将建立一种新型的 HBV-HCV 共感染免疫细胞培养系统。此外，还将研究 HBV-HCV 共感染对 cccDNA（HBV 持久性的重要储存库）的影响。将使用结构蛋白内含有突变的 HBV 构建体以及 HepaRG 细胞培养系统。