title: Modification of endothelial cell functions by Hantaan virus infection: prolonged hyper-permeability induced by TNF-alpha of hantaan virus-infected endothelial cell monolayers.
abstract: Serious vascular leakage is central to the pathogenesis of hantavirus infections. However, there is no evidence suggesting the hantavirus infection of endothelial cells directly causes obvious cell damage or morphological alteration either in vivo or in vitro. In this study, we examined whether Hantaan virus (HTNV) infection modifies the barrier function of endothelial cell monolayers upon the exposure to pro-inflammatory cytokines. Low levels (1 ng/ml) of tumor necrosis factor-alpha initially increased the permeability in both HTNV-infected and uninfected monolayers similarly. Thereafter, however, these monolayers showed significant difference. The HTNV-infected monolayers remained irreversibly hyper-permeable during the experimental period up to 4 days, while the uninfected monolayers completely recovered the barrier function. The prolonged hyper-permeability of HTNV-infected monolayers was not associated with cell death or gap formation in the monolayers, and was independent from their nitric oxide or prostaglandin production. These results are the first evidence that hantavirus infection modifies barrier function of endothelial cell monolayers and suggest that HTNV-infection of endothelial cells may contribute to the increased vascular leakage through the prolonged response to cytokines.
authors.affiliation: Department of Virology 1, National Institute of Infectious Diseases, Musashimurayama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Niikura
authors.forename: A
authors.initials: A
authors.lastname: Maeda
authors.forename: T
authors.initials: T
authors.lastname: Ikegami
authors.forename: M
authors.initials: M
authors.lastname: Saijo
authors.forename: I
authors.initials: I
authors.lastname: Kurane
authors.forename: S
authors.initials: S
authors.lastname: Morikawa
mesh_terms: D001896:Boron Compounds; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism* / Q000821:virology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism / Q000821:virology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D018063:Hantaan virus / Q000472:pathogenicity*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008689:Methacrylates; D008768:Methylmethacrylates; D009569:Nitric Oxide / Q000096:biosynthesis; D010539:Permeability; D011453:Prostaglandins / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*; D014471:Umbilical Veins; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D001896:Boron Compounds; D004791:Enzyme Inhibitors; D006146:Guanidines; D015850:Interleukin-6; D008689:Methacrylates; D008768:Methylmethacrylates; D011453:Prostaglandins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C049495:Super-bond; C004479:pimagedine; D007213:Indomethacin