title: Dengue virus infection of human endothelial cells leads to chemokine production, complement activation, and apoptosis.
abstract: Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) are severe complications of secondary dengue virus (DV) infection. Vascular leakage, hemorrhagic diathesis and complement activation are the hallmarks of the disease. The short-lived nature of the plasma leakage syndrome has led to the conclusion that altered permeability is most likely effected by a soluble mediator. In the present study, we show that infection of human endothelial cells with DV induces the transcriptional up-regulation and secretion of RANTES and IL-8 and, in the presence of anti-dengue Abs, the formation of nonlytic complement complexes. Extremely high levels of IL-8 were detected in plasma and pleural fluid samples from patients with DSS. Furthermore, DV infection of endothelial cells in vitro caused apoptosis. Complement activation, chemokine induction, and apoptotic cell death may act in concert to cause the fulminant but short-lived vascular leakage that is characteristic of DHF/DSS.
authors.affiliation: Institute of Medical Microbiology and Hygiene, Johannes Gutenberg University, Mainz, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Avirutnan
authors.forename: P
authors.initials: P
authors.lastname: Malasit
authors.forename: B
authors.initials: B
authors.lastname: Seliger
authors.forename: S
authors.initials: S
authors.lastname: Bhakdi
authors.forename: M
authors.initials: M
authors.lastname: Husmann
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D016923:Cell Death / Q000276:immunology; D002460:Cell Line; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis*; D003167:Complement Activation; D003716:Dengue Virus / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019595:Severe Dengue / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology; D014470:Umbilical Cord; D015854:Up-Regulation / Q000276:immunology
chemical_list: D018946:Chemokine CCL5; D018925:Chemokines; D016209:Interleukin-8; D016328:NF-kappa B