title: Bluetongue virus infection alters the impedance of monolayers of bovine endothelial cells as a result of cell death.
abstract: Bluetongue virus (BTV) is the cause of bluetongue, an emerging, arthropod-transmitted disease of ungulates. Bluetongue is characterized by vascular injury with hemorrhage, tissue infarction and widespread edema, lesions that are consistent with those of the so-called viral hemorrhagic fevers. To further investigate the pathogenesis of vascular injury in bluetongue, we utilized an electrical impedance assay and immunofluorescence staining to compare the effects of BTV infection on cultured bovine endothelial cells (bPAEC) with those of inducers of cell death (Triton X-100) and interendothelial gap formation (tissue necrosis factor [TNF]). The data confirm that the adherens junctions of BTV-infected bPAECs remained intact until 24h post-infection, and that loss of monolayer impedance precisely coincided with onset of virus-induced cell death. In contrast, recombinant bovine TNF-alpha caused rapid loss of bPAEC monolayer impedance that was associated with interendothelial gap formation and redistribution of VE-cadherin, but without early cell death. The data from these in vitro studies are consistent with a pathogenesis of bluetongue that involves virus-induced vascular injury leading to thrombosis, hemorrhage and tissue necrosis. However, the contribution of cytokine-induced interendothelial gap formation with subsequent edema and hypovolemic shock contributes to the pathogenesis of bluetongue remains to be fully characterized.
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, One Shields Ave., University of California, Davis, CA 95616, USA.
authors.forename: Clifton P
authors.initials: CP
authors.lastname: Drew
authors.forename: Ian A
authors.initials: IA
authors.lastname: Gardner
authors.forename: Christie E
authors.initials: CE
authors.lastname: Mayo
authors.forename: Eiko
authors.initials: E
authors.lastname: Matsuo
authors.forename: Polly
authors.initials: P
authors.lastname: Roy
authors.forename: N James
authors.initials: NJ
authors.lastname: MacLachlan
mesh_terms: D022005:Adherens Junctions / Q000473:pathology; D000818:Animals; D001819:Bluetongue / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D001820:Bluetongue virus / Q000472:pathogenicity*; D002417:Cattle; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017097:Electric Impedance; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology / Q000821:virology; D017830:Octoxynol / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D017830:Octoxynol