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

Expression of human factors CD81, claudin-1, scavenger receptor, and occludin in mouse hepatocytes does not confer susceptibility to HCV entry
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DOI:
10.2220/biomedres.32.143
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发表时间:
2011-04-01
影响因子:
1.2
通讯作者:
Miura, Naoyuki
Miura, Naoyuki
中科院分区:
医学4区
文献类型:
--
作者:
Hikosaka, Keisuke;Noritake, Hidenao;Miura, Naoyuki

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没有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。近年来研究发现,CD 81、claudin-1、清道夫受体B型和occludin是HCV进入肝细胞的重要因素。我们制作了表达这四种人类蛋白质的转基因小鼠(Alb-CCSO),并检查来自患者血清或HCV假颗粒(HCVpp)的HCV是否能够感染它们。在将来自患者血清的HCV注射到小鼠后,在小鼠血清中未检测到HCV。我们也没有发现HCVpp进入Alb-CCSO小鼠原代肝细胞的迹象。此外,将HCV感染的Hep 3B细胞与HCV抗性的原代小鼠肝细胞融合,融合细胞显示出比野生型Hep 3B细胞低35倍的感染性,表明原代小鼠肝细胞在HCVpp进入中具有抑制因子。我们的研究结果表明,人类因素的表达并不赋予HCV进入肝脏的易感性。
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 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.