Yeh Chau-Ting, Lai Hsin-Yu, Yeh Yung-Ju, Cheng Ju-Chien
Liver Research Unit, Chang Gung Medical Center, 199 Tung Hwa North Road, Taipei 105, Taiwan.
Biochem Biophys Res Commun. 2008 Jul 18;372(1):157-61. doi: 10.1016/j.bbrc.2008.05.018. Epub 2008 May 12.
Although human CD81 has been shown to be essential for hepatitis C virus (HCV) infection, non-hepatic cells or transgenic animals expressing human CD81 alone did not support HCV replication. Co-expression of other cofactors was thus necessary for HCV replication. Previously, a hepatic factor named Sip-L was found to support HCV replication in an otherwise non-permissive cell line. To understand the species specificity of hepatic factors required for HCV replication, mouse hepatoma cells co-expressing human CD81 and Sip-L (Hepa1-6-CD81-Sip-L cells) were subjected for HCV infection assay. It was discovered that Hepa1-6-CD81-Sip-L cells were permissive for HCV infection and replication. An animal model was thus established by subcutaneous injection of the permissive cells into nude mice to generate tumors. Viral passages could be achieved in these animals. The antiviral effects of interferon and sodium stibogluconate administrated as a single agent or in combination were demonstrated in this animal model.
尽管已证明人类CD81对丙型肝炎病毒（HCV）感染至关重要，但单独表达人类CD81的非肝细胞或转基因动物并不支持HCV复制。因此，其他辅助因子的共表达对于HCV复制是必要的。此前，发现一种名为Sip-L的肝脏因子可在原本不允许的细胞系中支持HCV复制。为了解HCV复制所需肝脏因子的物种特异性，对共表达人类CD81和Sip-L的小鼠肝癌细胞（Hepa1-6-CD81-Sip-L细胞）进行HCV感染试验。发现Hepa1-6-CD81-Sip-L细胞允许HCV感染和复制。因此，通过将允许感染的细胞皮下注射到裸鼠中以产生肿瘤，建立了一种动物模型。在这些动物中可以实现病毒传代。在此动物模型中证明了干扰素和葡萄糖酸锑钠单独或联合给药的抗病毒效果。
