Production of infectious hepatitis C virus in tissue culture from a cloned viral genome
Production of infectious hepatitis C virus in tissue culture from a cloned viral genome
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DOI：
10.1038/nm1268
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发表时间：
2005-07-01
期刊：
影响因子：
82.9
通讯作者：
Liang, TJ
中科院分区：
文献类型：
--
作者：
Wakita, T;Pietschmann, T;Liang, TJ
丙型肝炎病毒（HCV）感染会导致慢性肝脏疾病，是一个全球性的公共卫生问题。由于缺乏病毒培养系统，对HCV的详细分析一直受阻。从一名暴发性肝炎患者体内克隆出的JFH1基因型2a株的亚基因组复制子能在细胞培养中高效复制。在此我们表明，JFH1基因组在转染到人肝癌细胞系（Huh7）后能高效复制并支持病毒颗粒的分泌。这些颗粒的密度约为1.15 - 1.17克/毫升，呈球形，平均直径约为55纳米。分泌的病毒对Huh7细胞具有感染性，并且其感染性可被CD81特异性抗体以及慢性感染个体的免疫球蛋白所中和。细胞培养产生的HCV对黑猩猩具有感染性。该系统为研究病毒的生命周期以及制定抗病毒策略提供了一个强有力的工具。
Hepatitis C virus (HCV) infection causes chronic liver diseases and is a global public health problem. Detailed analyses of HCV have been hampered by the lack of viral culture systems. Subgenomic replicons of the JFH1 genotype 2a strain cloned from an individual with fulminant hepatitis replicate efficiently in cell culture. Here we show that the JFH1 genome replicates efficiently and supports secretion of viral particles after transfection into a human hepatoma cell line (Huh7). Particles have a density of about 1.15 - 1.17 g/ml and a spherical morphology with an average diameter of about 55 nm. Secreted virus is infectious for Huh7 cells and infectivity can be neutralized by CD81-specific antibodies and by immunoglobulins from chronically infected individuals. The cell culture - generated HCV is infectious for chimpanzee. This system provides a powerful tool for studying the viral life cycle and developing antiviral strategies.