Poduri C D
Department of Biotechnology, Indian Institute of Technology, Guwahati North Guwahati, Guwahati 781 039, Assam, India.
Indian J Exp Biol. 2003 Jun;41(6):549-62.
Hepatitis C virus (HCV), an RNA and a hepatotropic virus, is the leading cause of viral hepatitis worldwide. Infection with this virus causes a repertoire of liver diseases that include acute hepatitis, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC), in addition to a number of extra-hepatic manifestations such as lichen planus, oral cancer, etc. At present, patients infected with this virus are treated with interferon either alone or in combination with ribavirin, a guanosine-like nucleoside analog. However, response to this treatment has been rather disappointing. For about a decade, lack of an alternative animal model other than chimpanzee, and an efficient cell culture system that could support long-term replication of the virus, hampered research on HCV. Despite this, a significant amount of information with regard to the molecular biology of the virus is available using bacterial cloning-expression systems, and based on computer predictions and analysis. Recent discovery of a cellular receptor to which the virus binds, identification of efficient cell culture/cell-free systems, HCV replicons and the development of a chimeric mouse model, provide a platform to verify the existing knowledge about this virus in the coming years. Additionally these developments aid the researchers in identifying novel therapeutic agents, apart from allowing us to reassess the efficiency of the currently available therapeutics. Presented in this article are a review of existing information with regard to the molecular biology of the virus, immunodiagnostic assays, genomic heterogeneity and the role of the virus in hepatocellular carcinoma. Likely therapeutic strategies other than those currently available are also introduced.
丙型肝炎病毒(HCV)是一种RNA病毒,具有嗜肝性,是全球病毒性肝炎的主要病因。感染这种病毒会引发一系列肝脏疾病,包括急性肝炎、慢性肝炎、肝硬化和肝细胞癌(HCC),此外还会出现一些肝外表现,如扁平苔藓、口腔癌等。目前,感染该病毒的患者接受干扰素单药治疗或与利巴韦林(一种鸟苷类似物核苷类似物)联合治疗。然而,这种治疗的效果相当令人失望。大约十年间,除黑猩猩外缺乏其他替代动物模型,以及缺乏能够支持该病毒长期复制的高效细胞培养系统,阻碍了丙型肝炎病毒的研究。尽管如此,利用细菌克隆表达系统,并基于计算机预测和分析,已经获得了大量关于该病毒分子生物学的信息。最近发现了该病毒与之结合的细胞受体,鉴定出了高效的细胞培养/无细胞系统、丙型肝炎病毒复制子,并开发了嵌合小鼠模型,这些为在未来几年验证关于这种病毒的现有知识提供了一个平台。此外,这些进展有助于研究人员识别新型治疗药物,同时也使我们能够重新评估现有治疗方法的疗效。本文综述了关于该病毒分子生物学、免疫诊断检测、基因组异质性以及该病毒在肝细胞癌中的作用的现有信息。还介绍了目前可用治疗方法以外可能的治疗策略。