Dengue virus infection differentially regulates endothelial barrier function over time through type I interferon effects
Department of Medicine, Division of Infectious Diseases and Immunology; Center for Infectious Disease and Vaccine Research
Immunity | Immunology and Infectious Disease | Immunology of Infectious Disease | Infectious Disease
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.
DOI of Published Version
J Infect Dis. 2009 Jul 15;200(2):191-201. doi: 10.1086/599795. Link to article on publisher's site
The Journal of infectious diseases
Liu P, Woda M, Ennis FA, Libraty DH. (2009). Dengue virus infection differentially regulates endothelial barrier function over time through type I interferon effects. Infectious Diseases and Immunology Publications. https://doi.org/10.1086/599795. Retrieved from https://escholarship.umassmed.edu/infdis_pp/244