Einfluss von CD8 T-Zell-assoziiertem Selektionsdruck auf die Evolution des Hepatitis C Virus

CD8 T细胞相关选择压力对丙型肝炎病毒进化的影响

• 批准号: 27748077
• 负责人: Professor Dr. Jörg Timm
• 金额: --
• 依托单位: Institut für Virologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/27748077?language=en
• 关键词: Einfluss; von; CD8; Zell; assoziiertem

The hepatitis C virus (HCV) is a major cause of liver cirrhosis, liver failure and hepatocellular carcinoma, infecting an estimated 170 million individuals worldwide. The poor responsiveness to drug treatment, combined with limited access in the most critical regions of the world, has prompted efforts to develop an effective vaccine against HCV. Recent studies suggest that immune control of HCV is possible, specifically with cellular immune responses being essential for spontaneous resolution of acute HCV and protection from persistent infection in both humans and chimpanzees. The inherent sequence diversity of HCV represents one of the most substantial challenges to the development of an effective HCV vaccine. Not only does this pathogen continue to evolve in the host over the course of infection, but the global sequence diversity of HCV makes antigen selection for vaccines very difficult. In HIV and SIV, two other highly variable pathogens, numerous studies associate viral mutations with evasion of host antibody and CD8 T cell responses. The impact that this evolution can have on immune control can be profound. These studies are beginning to solidify our understanding of the role of host immune pressures in shaping the diversity of these pathogens. Therefore, understanding the relationship between HLA alleles, CD8 responses, and viral sequence diversity is necessary to elucidate the interaction between virus evolution and immune control of HCV, and help address the degree to which immune pressures are contributing to the global sequence diversity of HCV.

丙型肝炎病毒（HCV）是肝硬化、肝衰竭和肝细胞癌的主要原因，全世界估计感染1.7亿人。对药物治疗的反应性差，加上世界上最关键地区的获得有限，促使人们努力开发有效的HCV疫苗。最近的研究表明，HCV的免疫控制是可能的，特别是细胞免疫应答对于急性HCV的自发消退和保护人类和黑猩猩免受持续感染至关重要。HCV的固有序列多样性代表了开发有效HCV疫苗的最实质性挑战之一。不仅这种病原体在感染过程中在宿主中继续进化，而且HCV的全球序列多样性使得疫苗的抗原选择非常困难。在HIV和SIV这两种其他高度可变的病原体中，许多研究将病毒突变与逃避宿主抗体和CD8 T细胞应答联系起来。这种进化对免疫控制的影响可能是深远的。这些研究开始巩固我们对宿主免疫压力在塑造这些病原体多样性中的作用的理解。因此，了解HLA等位基因，CD8反应和病毒序列多样性之间的关系是必要的，以阐明病毒进化和HCV的免疫控制之间的相互作用，并帮助解决免疫压力在多大程度上有助于HCV的全球序列多样性。