Lv L, Kang Q, Yu X, Gao B, Hu T, Ma P, Zhang Y, Yan F, Xiao J, Deng J, Zhou X, Xu J
Acta Virol. 2015 Mar;59(1):20-6. doi: 10.4149/av_2015_01_20.
Development of mouse model of hepatitis C virus (HCV) infection has great significance in drug screening and vaccine research. The barriers of interspecies transmission of HCV are increasingly better understood. Human factors, namely low-density lipoprotein receptor (hLDLR), CD81 (hCD81), scavenger receptor class B type I (hSCARB1), occludin (hOCLN) and claudin 1 (hCLDN1) are all required for rendering mouse hepatocytes permissive to HCV. With the aim to humanize mouse hepatocytes we constructed two recombinant vectors tandemly expressing the first three and the last two HCV entry factors mentioned above, respectively. Cotransfection of mouse hepatocytes with these vectors made them permissive to HCV binding and entry. Tandem overexpression of hLDLR, hSCARB1, hCD81, hCLDN1 and hOCLN is a novel approach to tailoring mouse hepatocytes to HCV binding and entry which can be further used to establish a mouse model of HCV infection as a basis for developing antiviral drugs and vaccines.
丙型肝炎病毒（HCV）感染小鼠模型的建立在药物筛选和疫苗研究中具有重要意义。人们对HCV种间传播的障碍有了越来越深入的了解。人类因子，即低密度脂蛋白受体（hLDLR）、CD81（hCD81）、I型B类清道夫受体（hSCARB1）、闭合蛋白（hOCLN）和紧密连接蛋白1（hCLDN1），都是使小鼠肝细胞对HCV易感所必需的。为了使小鼠肝细胞人源化，我们构建了两个重组载体，分别串联表达上述前三个和后两个HCV进入因子。将这些载体与小鼠肝细胞共转染，使其对HCV结合和进入易感。hLDLR、hSCARB1、hCD81、hCLDN1和hOCLN的串联过表达是一种使小鼠肝细胞适应HCV结合和进入的新方法，可进一步用于建立HCV感染小鼠模型，作为开发抗病毒药物和疫苗的基础。
