HCV Research Group, School of Immunity and Infection, Institute of Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Expert Rev Anti Infect Ther. 2010 Sep;8(9):977-80. doi: 10.1586/eri.10.86.
Hepatitis C virus (HCV) infection spreads primarily via contact with infected blood and can establish a persistent infection in 80% of infected individuals, progressively causing chronic liver disease that can lead to hepatocellular carcinoma or end-stage liver disease requiring a transplant. There is no vaccine, and current treatment with interferon and ribavirin is costly, poorly tolerated and ineffective for a large proportion of patients. Technical limitations have stifled the study of HCV immunology, and hence the correlates of resolution remain elusive. HCV robustly infects hepatocytes in the liver, yet HCV RNA is often found to be associated with peripheral blood lymphocytes and extrahepatic manifestations of the disease include B-cell abnormalities. The few existing characterized viral clones that can replicate in vitro have consistently failed to infect immune cells; however, some groups have detected low levels of replication in peripheral blood cells, hinting that occult forms of infection may be possible. HCV lymphotropism remains a controversial subject that needs to be elucidated in order to identify viral reservoirs that may provide targets for therapeutic intervention. The precise interactions between HCV and immune cells need to be determined to establish if the virus has developed mechanisms to modulate immune responses. In the study by Durand et al., correlations were sought between cell tropism and mutations in the 5 noncoding region of the HCV genome, known as the internal ribosome entry site. Key findings are discussed here, highlighting current experimental challenges that surround the topic of HCV lymphotropism.
丙型肝炎病毒 (HCV) 感染主要通过接触受感染的血液传播，在 80%的感染者中可建立持续性感染，逐渐导致慢性肝病，可导致肝细胞癌或终末期肝病需要进行移植。目前尚无疫苗，干扰素和利巴韦林的现有治疗方法费用昂贵、耐受性差，且对很大一部分患者无效。技术限制阻碍了 HCV 免疫学的研究，因此，其解决的相关因素仍然难以捉摸。HCV 可在肝脏中强有力地感染肝细胞，但 HCV RNA 常与外周血淋巴细胞相关，疾病的肝外表现包括 B 细胞异常。少数现有的可在体外复制的特征性病毒克隆始终未能感染免疫细胞；然而，一些研究小组在外周血细胞中检测到低水平的复制，暗示可能存在隐匿性感染形式。HCV 的嗜淋巴性仍然是一个有争议的问题，需要加以阐明，以确定可能为治疗干预提供目标的病毒储库。需要确定 HCV 与免疫细胞之间的精确相互作用，以确定病毒是否已经开发出调节免疫反应的机制。在 Durand 等人的研究中，研究人员寻求细胞嗜性与 HCV 基因组 5'非编码区（称为内部核糖体进入位点）突变之间的相关性。本文重点讨论了关键发现，强调了围绕 HCV 嗜淋巴性主题的当前实验挑战。
