Sec24C-Dependent Transport of Claudin-1 Regulates Hepatitis C Virus Entry
Sec24C-Dependent Transport of Claudin-1 Regulates Hepatitis C Virus Entry
复制标题
Claudin-1 的 Sec24C 依赖性转运调节丙型肝炎病毒进入
DOI：
10.1128/jvi.00629-17
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发表时间：
2017-09-01
影响因子：
5.4
通讯作者：
Zhang, Leiliang
中科院分区：
文献类型：
--
作者：
Yin, Peiqi;Li, Ye;Zhang, Leiliang
Claudin-1是丙型肝炎病毒（HCV）进入机体所必需的辅助受体。虽然广泛的研究集中在claudin-1作为抗HCV的目标，很少有人知道如何在细胞表面的claudin-1的水平是由宿主囊泡运输调节。在这里，我们确定了封闭蛋白-1和Sec 24 C之间的相互作用，Sec 24 C是外壳蛋白复合物II（COPII）囊泡运输系统的货物分选组分。通过与Sec 24 C通过其C-末端YV相互作用，claudin-1从内质网（ER）转运并最终靶向细胞表面。阻断COPII转运通过降低细胞表面的claudin-1水平来抑制HCV进入。这些发现提供了深入了解COPII囊泡转运在HCV进入中的作用的机制。紧密连接蛋白claudin-1是丙型肝炎病毒的细胞受体之一，全球有1.85亿人感染丙型肝炎病毒。其细胞分布在HCV进入中起重要作用;然而，尚不清楚claudin-1在细胞表面的定位如何由宿主转运途径控制。在本文中，我们不仅确定了Sec 24 C作为HCV进入的关键宿主因子，而且还发现了COPII机制将claudin-1转运到细胞表面的新机制。这种机制可能会扩展到其他含有C-末端YV或V基序的claudin。
ABSTRACT Claudin-1 is a hepatitis C virus (HCV) coreceptor required for viral entry. Although extensive studies have focused on claudin-1 as an anti-HCV target, little is known about how the level of claudin-1 at the cell surface is regulated by host vesicular transport. Here, we identified an interaction between claudin-1 and Sec24C, a cargo-sorting component of the coat protein complex II (COPII) vesicular transport system. By interacting with Sec24C through its C-terminal YV, claudin-1 is transported from the endoplasmic reticulum (ER) and is eventually targeted to the cell surface. Blocking COPII transport inhibits HCV entry by reducing the level of claudin-1 at the cell surface. These findings provide mechanistic insight into the role of COPII vesicular transport in HCV entry. IMPORTANCE Tight junction protein claudin-1 is one of the cellular receptors for hepatitis C virus, which infects 185 million people globally. Its cellular distribution plays important role in HCV entry; however, it is unclear how the localization of claudin-1 to the cell surface is controlled by host transport pathways. In this paper, we not only identified Sec24C as a key host factor for HCV entry but also uncovered a novel mechanism by which the COPII machinery transports claudin-1 to the cell surface. This mechanism might be extended to other claudins that contain a C-terminal YV or V motif.