Grupo Medicina Molecular y de Translación - Facultad de Medicina, Universidad de Antioquia, Medellín, 050010, Colombia.
RNómica Teórica y Computacional - Facultad de Ciencias, Universidad Nacional de Colombia, Bogotá, 111321, Colombia.
Virus Res. 2019 Jan 2;259:68-76. doi: 10.1016/j.virusres.2018.10.018. Epub 2018 Oct 25.
The most life-threatening effect of the Dengue virus (DENV) infection is an acute destabilization of the microvascular endothelial cell (MEC) barrier leading to plasma leakage, hypovolemic shock and haemorrhage. However, the underlying cellular mechanisms responsible for the dysfunction of MECs are not well understood. To identify potential cellular processes altered during DENV infection of MECs, expression profiles of cytokines/growth factors and microRNAs were measured by Luminex assay and next generation sequencing, respectively. Synchronously DENV2-infected MECs increase the secretion of IL-6, IL-8, FGF-2, GM-CSF, G-CSF, TGF-α, GRO, RANTES, MCP-1 and MCP-3. Conditioned media of infected MECs increased the migration of non-infected MECs. Furthermore, six miRNAs deregulated at 24 hpi were predicted to regulate host genes involved in cell migration and vascular developmental processes such as angiogenesis. These in silico analyses provide insights that support that DENV promotes an acute migratory phenotype in MECs that contributes to the vascular destabilization observed in severe dengue cases.
登革热病毒（DENV）感染最致命的影响是微脉管内皮细胞（MEC）屏障的急性失稳，导致血浆渗漏、低血容量性休克和出血。然而，导致 MEC 功能障碍的潜在细胞机制尚不清楚。为了确定在 DENV 感染 MEC 过程中改变的潜在细胞过程，通过 Luminex 分析和下一代测序分别测量细胞因子/生长因子和 microRNA 的表达谱。同时感染的 MEC 增加了 IL-6、IL-8、FGF-2、GM-CSF、G-CSF、TGF-α、GRO、RANTES、MCP-1 和 MCP-3 的分泌。感染的 MEC 的条件培养基增加了未感染的 MEC 的迁移。此外，在 24 hpi 下调的六种 microRNA 被预测可调节参与细胞迁移和血管发育过程（如血管生成）的宿主基因。这些计算机分析提供了支持 DENV 在严重登革热病例中观察到的血管不稳定促进 MEC 中急性迁移表型的见解。
