Sklan Ella H, Charuworn Prista, Pang Philip S, Glenn Jeffrey S
Department of Clinical Immunology and Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Nat Rev Gastroenterol Hepatol. 2009 Apr;6(4):217-27. doi: 10.1038/nrgastro.2009.32.
HCV infection is an important cause of liver disease worldwide-nearly 80% of infected patients develop chronic liver disease, which leads to the development of liver cirrhosis and hepatocellular carcinoma. The ability of HCV to persist within a host is believed to be related to the numerous mechanisms by which it evades the immune response of the host. These mechanisms can be divided into defensive and offensive strategies. Examples of defensive mechanisms include replication within enclosed structures, which provides protection from the host's antiviral defenses, genetic diversity created by inaccurate replication, which yields mutants resistant to the cell's antiviral strategies, and association of the virion with protective lipoproteins. Offensive mechanisms include virally encoded proteins and other factors that disrupt the ability of the host cells to detect the virus and downregulate its ability to respond to interferon, impair innate immune defense mechanisms and alter T-cell responses, and prevent the development of an effective B-cell-mediated humoral response. Greater understanding of these viral survival strategies will ultimately translate into more effective antiviral therapies and better prognosis for patients.
丙型肝炎病毒(HCV)感染是全球肝脏疾病的一个重要病因——近80%的感染者会发展为慢性肝病,进而导致肝硬化和肝细胞癌。HCV在宿主体内持续存在的能力被认为与它逃避宿主免疫反应的多种机制有关。这些机制可分为防御策略和进攻策略。防御机制的例子包括在封闭结构内复制,这为病毒提供了免受宿主抗病毒防御的保护;由不准确复制产生的基因多样性,产生对细胞抗病毒策略有抗性的突变体;以及病毒粒子与保护性脂蛋白的结合。进攻机制包括病毒编码的蛋白质和其他因素,这些因素会破坏宿主细胞检测病毒的能力,下调其对干扰素的反应能力,损害先天性免疫防御机制并改变T细胞反应,以及阻止有效的B细胞介导的体液反应的发展。对这些病毒生存策略的更深入了解最终将转化为更有效的抗病毒治疗方法,并为患者带来更好的预后。