Dengue virus infection differentially regulates endothelial barrier function over time through type I interferon effects
UMass Chan Affiliations
Center for Infectious Disease and Vaccine ResearchDepartment of Medicine, Division of Infectious Diseases and Immunology
Document Type
Journal ArticlePublication Date
2009-07-15Keywords
ImmunityImmunology and Infectious Disease
Immunology of Infectious Disease
Infectious Disease
Metadata
Show full item recordAbstract
BACKGROUND: The morbidity and mortality resulting from dengue hemorrhagic fever (DHF) are largely caused by endothelial barrier dysfunction and a unique vascular leakage syndrome. The mechanisms that lead to the location and timing of vascular leakage in DHF are poorly understood. We hypothesized that direct viral effects on endothelial responsiveness to inflammatory and angiogenesis mediators can explain the DHF vascular leakage syndrome. METHODS: We used an in vitro model of human endothelium to study the combined effects of dengue virus (DENV) type 2 (DENV2) infection and inflammatory mediators on paracellular macromolecule permeability over time. RESULTS: Over the initial 72 h after infection, DENV2 suppressed tumor necrosis factor (TNF)-alpha-mediated hyperpermeability in human umbilical vein endothelial cell (HUVEC) monolayers. This suppressive effect was mediated by type I interferon (IFN). By 1 week, TNF-alpha stimulation of DENV2-infected HUVECs synergistically increased cell cycling, angiogenic changes, and macromolecule permeability. This late effect could be prevented by the addition of exogenous type I IFN. CONCLUSIONS: DENV infection of primary human endothelial cells differentially modulates TNF-alpha-driven angiogenesis and hyperpermeability over time. Type I IFN plays a central role in this process. Our findings suggest a rational model for the DHF vascular leakage syndrome.Source
J Infect Dis. 2009 Jul 15;200(2):191-201. doi: 10.1086/599795. Link to article on publisher's siteDOI
10.1086/599795Permanent Link to this Item
http://hdl.handle.net/20.500.14038/35028PubMed ID
19530939Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1086/599795