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人源因子CD81、紧密连接蛋白-1、清道夫受体和闭合蛋白在小鼠肝细胞中的表达不会使细胞对丙型肝炎病毒(HCV)的进入产生易感性。

Expression of human factors CD81, claudin-1, scavenger receptor, and occludin in mouse hepatocytes does not confer susceptibility to HCV entry.

作者信息

Hikosaka Keisuke, Noritake Hidenao, Kimura Wataru, Sultana Nishat, Sharkar Mohammad T K, Tagawa Yoh-Ichi, Uezato Tadayoshi, Kobayashi Yoshimasa, Wakita Takaji, Miura Naoyuki

机构信息

Department of Biochemistry, Hamamatsu University School of Medicine, Handa-yama, Higashi-ku, Hamamatsu, Shizuoka, Japan.

出版信息

Biomed Res. 2011 Apr;32(2):143-50. doi: 10.2220/biomedres.32.143.

Abstract

No suitable mouse model is available for studying chronic liver disease caused by hepatitis C virus (HCV). CD81, claudin-1, scavenger receptor class B type I, and occludin were recently reported to be the important factors in HCV entry into hepatocytes. We made transgenic mice (Alb-CCSO) expressing the four human proteins and examined whether HCV from a patient serum or HCV pseudoparticles (HCVpp) were capable of infecting them. HCV was not detected in the mouse serum after injecting the mice with HCV from a patient serum. We also found no indications of HCVpp entry into primary hepatocytes from Alb-CCSO mice. In addition, HCV-infectible Hep3B cells were fused with HCV-resistant primary mouse hepatocytes and the fused cells showed 35-fold lower infectivity compared to wild-type Hep3B cells, indicating that primary mouse hepatocytes have the inhibitory factor(s) in HCVpp entry. Our results suggest that the expression of the human factors does not confer susceptibility to HCV entry into the liver.

摘要

目前尚无合适的小鼠模型可用于研究丙型肝炎病毒(HCV)引起的慢性肝病。最近有报道称,CD81、紧密连接蛋白-1、B类I型清道夫受体和闭合蛋白是HCV进入肝细胞的重要因素。我们制备了表达这四种人类蛋白的转基因小鼠(Alb-CCSO),并检测来自患者血清的HCV或HCV假病毒颗粒(HCVpp)是否能够感染它们。给小鼠注射来自患者血清的HCV后,在小鼠血清中未检测到HCV。我们还未发现HCVpp进入Alb-CCSO小鼠原代肝细胞的迹象。此外,将可被HCV感染的Hep3B细胞与对HCV具有抗性的原代小鼠肝细胞融合,与野生型Hep3B细胞相比,融合细胞的感染性降低了35倍,这表明原代小鼠肝细胞中存在抑制HCVpp进入的因子。我们的结果表明,人类因子的表达并未使肝脏对HCV进入产生易感性。

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