登革病毒（DV）感染引起的重症登革热（sDF）是威胁患者生命的急症，其主要临床特点是微血管通透性增加引起出血和休克。血管内皮细胞（VECs）是维持微血管完整性的重要组分，也是DV的靶细胞之一。但DV感染VECs引起通透性增加的机制尚不清楚。以往我们已证明：VECs表达的整合素β3能够与DV相互作用，介导DV进入的同时，参与VECs通透性的调控。为此本项目拟：（1）明确与整合素β3相互作用的主要病毒蛋白；（2）利用DV1-4的假病毒颗粒，研究包膜结构蛋白与整合素β3的相互作用及其与血清型的关联；（3）表达、纯化包膜E蛋白的3个功能区，检测其与整合素β3的亲和力，确定其相互作用的结构域；（4）设计并合成小分子肽，研究其与整合素β3的亲和力和阻断感染的作用，确定E蛋白与整合素β3的作用位点。为阐明DV感染所致的sDF发生机制和靶向抗病毒药物的研发提供重要实验依据。

Infection by dengue virus (DV) can cause dengue fever (DF) and severe DF（sDF）, which is a more severe, sometimes lethal disease including dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). The plasma leakage and bleeding induced by increased vascular permeability are main clinical characters of sDF. However, the factors involved in the increased vascular permeability caused by DV infection are not understood. Vascular endothelial cells (VECs) are major components in maintaining micro-vascular permeability and also act as one of DV target cells. Previously we have found that integrin β3, which distribute largely on the surface of VECs, was associated with the entry of DV2 into VECs. Therefore, to further investigate the mechanism invovled in the interaction between DV and VECs mainly focusing on role of integrinβ3 during the viral entry, the following experiments will be performed in this study: (1) screening main viral proteins interacting with integrin β3; (2) using virus-like particle(VLP) of DV to investigate the interaction between structural proteins and integrinβ3 as well as its correlaion with DV serotypes; (3) based on expressing different domains of E protein, investigating interaction between major domain(s) of E protein and integrinβ3; (4) using synthetic peptides, investigating its inhibitory effect on viral entry into host cells to determine binding sites between peptides of E protein and integrinβ3. The results from this study will be available for further clarifying occurrence of sDF and for development of anti-viral drug.