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

严重流感中出现的血管内皮细胞高渗透性是基于流感病毒感染破坏了细胞之间的黏附连接。在这项研究中，我们揭示了感染甲型流感病毒(PR8)的人静脉内皮细胞高通透性的机制。随着血管高通透性的增加，内皮-钙粘附素细胞黏附复合体的关键调节成分β-连环蛋白的水平显著降低。由于GSK-3β对β-连环素N端的磷酸化是蛋白酶体依赖降解的起始步骤，因此我们研究了RNAi对GSK-3β的抑制作用。在GSK-3β基因敲除细胞中，IAV感染诱导的β-连环蛋白降解被显著抑制。这些结果表明，IAV感染诱导了GSK-3β介导的黏附连接中β-连环素的降解，并诱导了血管的高通透性。

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.