Thimme Robert, Neumann-Haefelin Christoph, Boettler Tobias, Blum Hubert E
Department of Medicine II, University Hospital Freiburg, D-79106 Freiburg, Germany.
Biol Chem. 2008 May;389(5):457-67. doi: 10.1515/bc.2008.061.
Hepatitis C virus (HCV) causes chronic infection in approximately two-thirds of cases, leading to chronic hepatitis, liver cirrhosis, liver disease, liver failure, and hepatocellular carcinoma in a substantial proportion of the 170 million HCV-infected individuals worldwide. It is generally accepted that the cellular immune response plays the most important role in determining the outcome of HCV infection. First, vigorous, multispecific and sustained CD4+ and CD8+ T-cell responses are associated with viral clearance. Second, depletion studies in chimpanzees, the only other host of HCV besides humans, have shown that both CD4+ and CD8+ T-cells are required for virus elimination. Third, the host's human leukocyte antigen alleles, which restrict the repertoire of CD4+ and CD8+ T-cell responses, influence the outcome of infection. Of note, protective immunity has been demonstrated in population-based studies, as well as in experimentally infected chimpanzees. Thus, a detailed understanding of the mechanisms contributing to the failure of the antiviral immune response should allow successful development of prophylactic and therapeutic vaccination strategies.
丙型肝炎病毒（HCV）在大约三分之二的病例中会引发慢性感染，在全球1.7亿HCV感染者中，相当一部分人会因此患上慢性肝炎、肝硬化、肝病、肝衰竭和肝细胞癌。人们普遍认为，细胞免疫反应在决定HCV感染的结果方面起着最重要的作用。首先，强烈、多特异性且持续的CD4+和CD8+ T细胞反应与病毒清除相关。其次，在黑猩猩（HCV除人类外的唯一其他宿主）身上进行的耗竭研究表明，病毒清除需要CD4+和CD8+ T细胞。第三，宿主的人类白细胞抗原等位基因限制了CD4+和CD8+ T细胞反应的范围，影响感染结果。值得注意的是，基于人群的研究以及实验感染的黑猩猩都证明了保护性免疫的存在。因此，详细了解导致抗病毒免疫反应失败的机制应有助于成功开发预防性和治疗性疫苗接种策略。
