Dengue virus (DENV) continues to be a major public health problem. DENV infection will cause mild dengue and severe dengue. Severe dengue is clinically manifested as serious complications, including dengue hemorrhagic fever and/or dengue shock syndrome (DHF/DSS), which is mainly characterized by vascular leakage. Currently, the pathogenesis of severe dengue is not elucidated thoroughly, and there are no known therapeutic targets for controlling the disease effectively. This study aimed to further reveal the potential molecular mechanism of severe dengue. In this study, the long non-coding RNA, ERG-associated lncRNA (lncRNA-ERGAL), was activated and significantly up-regulated in DENV-infected vascular endothelial cells. After knockdown of lncRNA-ERGAL, the expression of ERG, VE-cadherin, and claudin-5 was repressed; besides, cell apoptosis was enhanced, and cytoskeletal remodeling was disordered, leading to instability and increased permeability of vascular endothelial barrier during DENV infection. Fluorescence in situ hybridization (FISH) assay showed lncRNA-ERGAL to be mainly expressed in the cytoplasm. Moreover, the expression of miR-183-5p was found to increase during DENV infection and revealed to regulate ERG, junction-associated proteins, and the cytoskeletal structure after overexpression and knockdown. Then, ERGAL was confirmed to interact with miR-183-5p by luciferase reporter assay. Collectively, ERGAL acted as a miRNA sponge that can promote stability and integrity of vascular endothelial barrier during DENV infection via binding to miR-183-5p, thus revealing the potential molecular mechanism of severe dengue and providing a foundation for a promising clinical target in the future.

登革热病毒 (DENV) 仍然是一个主要的公共卫生问题。DENV 感染会引起轻度登革热和重度登革热。重症登革热在临床上表现为严重的并发症，包括登革出血热和/或登革休克综合征（DHF/DSS），主要表现为血管渗漏。目前，重症登革热的发病机制尚未完全阐明，也没有已知的有效控制该疾病的治疗靶点。本研究旨在进一步揭示重症登革热的潜在分子机制。在这项研究中，长链非编码 RNA、ERG 相关 lncRNA (lncRNA-ERGAL) 在 DENV 感染的血管内皮细胞中被激活并显着上调。lncRNA-ERGAL敲低后，ERG、VE-cadherin和claudin-5的表达被抑制；除了，细胞凋亡增强，细胞骨架重塑紊乱，导致 DENV 感染期间血管内皮屏障的不稳定和通透性增加。荧光原位杂交（FISH）测定显示lncRNA-ERGAL主要在细胞质中表达。此外，发现 miR-183-5p 的表达在 DENV 感染期间增加，并显示在过表达和敲低后调节 ERG、连接相关蛋白和细胞骨架结构。然后，通过荧光素酶报告基因分析证实 ERGAL 与 miR-183-5p 相互作用。总的来说，ERGAL 作为一种 miRNA 海绵，可以通过与 miR-183-5p 结合来促进 DENV 感染期间血管内皮屏障的稳定性和完整性，从而揭示重症登革热的潜在分子机制，并为有希望的临床靶点提供基础。未来。