The analysis of host response determining the severe influenza and HIV infection.

在严重流感中观察到的血管内皮细胞通透性过高是基于流感病毒感染破坏细胞之间的粘附连接。在本研究中，我们发现，在感染A型流感病毒（PR 8）的人静脉内皮细胞的高渗透性的机制，β连环蛋白，内皮细胞-钙粘蛋白细胞粘附复合物的关键调节成分，在感染过程中的水平显着下降，血管通透性增加。 由于GSK-3 β对β-连环蛋白的N-末端磷酸化是蛋白酶体依赖性降解的起始步骤，我们研究了RNAi抑制GSK-3 β的作用。IAV感染诱导的β-连环蛋白降解在GSK-3 β-敲低细胞中被显著抑制。这些结果表明，IAV感染诱导GSK-3 β介导的β-连环蛋白降解的粘附连接，并诱导血管通透性增高。

The vascular endothelial cell hyperpermeability seen in severe influenza is based on the disruption of adherence junctions between cells by influenza virus infection. In this study, we have shown the mechanisms of hyperpermeability of human vein endothelial cells infected with influenza A virus (PR8).The levels of beta catenin, a key regulatory component of the endothelial-cadherin cell adhesion complex, were markedly decreased during infection with increment of vascular hyperpermeability. Since the N-terminus phosphorylation of beta-catenin by GSK-3beta is the initiation step of proteasome-dependent degradation, we examined the effects of GSK-3beta suppression by RNAi. IAV infection-induced beta-catenin degradation was significantly inhibited in GSK-3beta-knockdown cells. These findings suggest that IAV infection induces GSK-3beta-mediated beta-catenin degradation in the adherence junctions and induces vascular hyperpermeability.