The tight junction proteins claudin-1,-6, and-9 are entry cofactors for hepatitis C virus
The tight junction proteins claudin-1,-6, and-9 are entry cofactors for hepatitis C virus
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DOI：
10.1128/jvi.01977-07
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发表时间：
2008-04-01
影响因子：
5.4
通讯作者：
Dragic, Tatjana
中科院分区：
文献类型：
--
作者：
Meertens, Laurent;Bertaux, Claire;Dragic, Tatjana
丙型肝炎病毒（HCV）是人类肝脏疾病的主要原因。 CD81四跨膜蛋白对于HCV渗透到肝细胞是必需的，但还不够，最近有报道称，紧密连接蛋白claudin-1是HCV进入肝细胞的关键辅助因子。在这里，我们确认了claudin-1在HCV进入中的作用。此外，我们发现CD81+细胞中表达的claudin-6和claudin-9也使得来自六种主要基因型的HCV假颗粒能够进入。尽管claudin-1、-6和-9在内皮细胞中作为进入辅助因子的功能相同，但claudin-1在肝癌细胞中更有效。这表明额外的细胞因子调节密蛋白作为 HCV 进入辅助因子的能力。我们的工作产生了新颖且重要的方法来研究 HCV 渗透到肝细胞的机制以及密蛋白家族在 HCV 传播、复制和发病机制中的作用。
Hepatitis C virus (HCV) is a major cause of liver disease in humans. The CD81 tetraspanin is necessary but not sufficient for HCV penetration into hepatocytes, and it was recently reported that the tight junction protein claudin-1 is a critical HCV entry cofactor. Here, we confirm the role of claudin-1 in HCV entry. In addition, we show that claudin-6 and claudin-9 expressed in CD81(+) cells also enable the entry of HCV pseudoparticles derived from six of the major genotypes. Whereas claudin-1, -6, and -9 function equally well as entry cofactors in endothelial cells, claudin-1 is more efficient in hepatoma cells. This suggests that additional cellular factors modulate the ability of claudins to function as HCV entry cofactors. Our work has generated novel and essential means to investigate the mechanism of HCV penetration into hepatocytes and the role of the claudin protein family in HCV dissemination, replication, and pathogenesis.