Dengue Viral Protease Interaction with NF-κB Inhibitor α/β Results in Endothelial Cell Apoptosis and Hemorrhage Development

摘要: Hemorrhagic manifestations occur frequently accompanying a wide range of dengue disease syndromes. Much work has focused on the contribution immune factors to pathogenesis hemorrhage, but how virus (DENV) participates in pathogenic process never been explored. Although there is no consensus that apoptosis basis vascular permeability human infections, we showed hemorrhage mouse model endothelial cell important development mice. To explore molecular DENV death, show this study protease interacts with cellular IκBα and IκBβ cleaves them. By inducing cleavage IκB kinase activation, activates NF-κB, which results death. Intradermal inoculation packaged adenovirus-associated virus-9 induces death dermal H51 activity site not involved interaction between IκB-α/β, enzymatic critical ability induce trigger development. Moreover, overexpression or protects cells from DENV-induced apoptosis. In study, discover be new targets are cleaved by protease.