title: Dengue virus type 2 modulates endothelial barrier function through CD73.
abstract: Dengue hemorrhagic fever is characterized by a unique vascular leakage syndrome. The mechanisms of endothelial barrier dysfunction in dengue hemorrhagic fever are not well understood. We examined the modulation of endothelial barrier function in dengue virus type 2 (DENV2) infections using primary human umbilical vein endothelial cells. We demonstrated that the increase in endothelial barrier function within 72 hours after DENV2 infection is mediated by type I interferon-dependent CD73 up-regulation. After 72 hours, DENV2 slowed the recovery of endothelial barrier function in response to tumor necrosis factor-α or vascular endothelial growth factor. This phenomenon was likely caused by type I interferon receptor signaling inhibition and lower CD73 levels in DENV2-infected endothelial cells. Our findings suggest that during DENV2 infection, endothelial barrier homeostasis is maintained by a balance between pro-inflammatory and pro-angiogenic cytokines, and type I interferon-dependent CD73 expression and activity.
authors.forename: Chinmay
authors.initials: C
authors.lastname: Patkar
authors.forename: Kris
authors.initials: K
authors.lastname: Giaya
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Libraty
mesh_terms: D015720:5'-Nucleotidase / Q000276:immunology*; D002478:Cells, Cultured; D003716:Dengue Virus / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans
chemical_list: D015720:5'-Nucleotidase