COPII调节丙肝病毒进入的机制

Claudin-1是丙肝病毒进入宿主细胞所必需的受体之一，其细胞表面定位对于claudin-1发挥丙肝病毒受体功能非常重要。宿主囊泡运输调节claudin-1的细胞表面定位机制尚有待研究。基于前期研究，本项目提出的科学假设是：丙肝病毒受体claudin-1通过羧基端YV与COPII负责货物分选的关键分子Sec24C结合，经COPII通路从内质网运输到高尔基体，最终到达细胞表面。抑制COPII通路可能会减少claudin-1在细胞表面分布，进而抑制丙肝病毒进入细胞。本项目研究内容包括：(1) 确定claudin-1与Sec24C相互作用；(2)阐明claudin-1的细胞表面定位是否依赖于COPII；(3)阐明COPII是否影响丙肝病毒进入。本项目的研究将可以揭示claudin-1是COPII的货物，阐明COPII调控病毒进入的机制，对于丙肝病毒进入的细胞生物学研究具有重要的理论价值。

Claudin-1 is a HCV co-receptor required for viral entry. While extensive studies have focused on claudin-1 as an anti-HCV target, little is known about how surface level of claudin-1 is regulated by host vesicular transport. Based on our preliminary results, we propose the following hypothesis. By interacting with the cargo sorting component of the COPII vesicular transport through C terminal YV, claudin-1 is transported from ER to golgi, eventually to plasma membrane. Blocking COPII transport will inhibit HCV entry through reducing surface level of claudin-1. To test this hypothesis, we propose three specific aims. Aim 1: we will define the interaction between claudin-1 and Sec24C. Aim 2: we will explore the mechanism how COPII regulates surface localization of claudin-1. Aim 3: we will elucidate how COPII regulates HCV entry. Our work will shed mechanistic insight on how HCV entry is regulated by COPII vesicular transport.