Fig. 1

Dengue virus interactions with macrophages and endothelial cells that lead to hemorrhage development. a Inoculation by mosquito bite of DENV (DV) into the skin. b The virus infects several cell types including endothelial cells (ECs). c DENV induces production of chemokines that attract macrophages. d DENV stimulates macrophages to produce TNF. e DENV NS2B/3 protease interacts with and cleaves cellular IκBα/IκBβ. DENV NS2B/3 protease also activates IKK, which phosphorylates IκBα and IκBβ. IκBα/IκBβ cleavage enables p50 and p65 translocation into the nucleus, thereby activating NF-κB which results in endothelial cell death. f The presence of TNF in the microenvironment enhances DENV-primed EC apoptosis. Endothelium damage/increased vascular permeability results in hemorrhage development. Solid arrows represent events that enhance endothelium damage. Dotted arrow indicates an event that is speculated to occur [30, 58, 65]