A novel virus culture system for hepatitis C virus

A novel virus culture system for hepatitis C virus
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DOI:
10.2217/17460794.1.4.519
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发表时间:
2006-07
期刊:
影响因子:
3.1
通讯作者:
Takanobu Kato;T. Date;M. Miyamoto;T. Wakita
Takanobu Kato;T. Date;M. Miyamoto;T. Wakita
中科院分区:
医学4区
文献类型:
--
作者:
Takanobu Kato;T. Date;M. Miyamoto;T. Wakita

文献摘要

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丙型肝炎病毒是引起输血后和散发性急性肝炎的主要原因。丙型肝炎病毒感染持续存在并导致慢性肝病,包括肝硬变和肝细胞癌。尽管丙型肝炎病毒很重要,但由于缺乏适当的体外病毒培养系统,人们对其生命周期的了解一直受到阻碍。我们从一名重型肝炎患者中分离了JFH-1株的全长丙型肝炎病毒基因,并构建了JFH-1亚基因组复制子,该复制子在培养细胞中有效复制,没有适应性突变。将全长RNA转录本导入Huh7细胞,获得了JFH-1 RNA的高效复制和重组病毒颗粒的分泌。分泌的病毒颗粒对培养细胞和黑猩猩具有传染性。这些病毒颗粒对允许细胞系的感染性比对原始Huh7细胞系更大。该感染性丙型肝炎病毒系统是研究丙型肝炎病毒生活史和发展丙型肝炎病毒的有力工具。
Hepatitis C virus (HCV) is a principal cause of post-transfusion and sporadic acute hepatitis. HCV infection persists and causes chronic liver diseases, including cirrhosis and hepatocellular carcinoma. Despite HCV’s importance, understanding of its life cycle has been hampered by the lack of an appropriate in vitro viral culture system. We isolated full-length HCV cDNA of the JFH-1 strain from a fulminant hepatitis patient, and constructed a JFH-1 subgenomic replicon that replicated efficiently in cultured cells without adaptive mutations. Full-length RNA transcripts were transfected into Huh7 cells, resulting in efficient replication of JFH-1 RNA and secretion of recombinant viral particles into the culture medium. The secreted viral particles were infectious for cultured cells and in a chimpanzee. The infectivity of these viral particles was greater for permissive cell lines than for original Huh7 cell lines. This infectious HCV system is a powerful tool for studying the HCV life cycle and for developi...