THE INTERPLAY OF CELLULAR HOST FACTORS AND VIRAL FACTORS IN MEDIATING VASCULAR PERMEABILITY DURING DENGUE VIRUS INFECTION

Abstract

Dengue virus (DV)2-infection of HUVEC resulted in endothelial hyperpermeability with the down-regulation of Ang1 and up-regulation of Ang2 proteins expression. Addition of rAng1 to DV-infected HUVEC prevented endothelial hyperpermeability. The imbalance of Ang1 and 2 may play a role in mediating endothelial hyperpermeability in DV2-infected HUVEC. PKC e was activated during DV2-infection and knock-down of PKC e prevented DV2-induced endothelial hyperpermeability and inhibition of PKC e prevents DV2-induced Ang1/Ang2 protein imbalance. These findings suggest the role of PKC e in mediating endothelial hyperpermeability during DV2-infection. DV2-infection of K562 and PBM induced the translocation of HMGB1 from the nuclei to the cytoplasm. The translocation is mediated by DV capsid involving PCAF acetylase complex in K562 cells. HMGB1 is then released from DV-infected monocytes into the extracellular milieu. Application of DV- infected K562 cell culture supernatants to HUVEC induced endothelial hyperpermeability which can be prevented by co-treatment with HMGB1 neutralizing antibody.