title: Strain-dependent effects of clinical echovirus 30 outbreak isolates at the blood-CSF barrier
creator: Dahm, Tobias
creator: Adams, Ortwin
creator: Boettcher, Sindy
creator: Diedrich, Sabine
creator: Morozov, Vasily
creator: Hansman, Grant
creator: Fallier-Becker, Petra
creator: Schädler, Sebastian
creator: Burkhardt, Claus J.
creator: Weiss, Christel
creator: Stump-Guthier, Carolin
creator: Ishikawa, Hiroshi
creator: Schroten, Horst
creator: Schwerk, Christian
creator: Tenenbaum, Tobias
creator: Rudolph, Henriette
subject: 570
subject: 570 Life sciences
subject: 610
subject: 610 Medical sciences Medicine
description: Background: Echovirus (E) 30 (E-30) meningitis is characterized by neuroinflammation involving immune cell pleocytosis at the protective barriers of the central nervous system (CNS). In this context, infection of the blood-cerebrospinal fluid barrier (BCSFB), which has been demonstrated to be involved in enteroviral CNS pathogenesis, may affect the tight junction (TJ) and adherens junction (AJ) function and morphology.    Methods: We used an in vitro human choroid plexus epithelial (HIBCPP) cell model to investigate the effect of three clinical outbreak strains (13-311, 13-759, and 14-397) isolated in Germany in 2013, and compared them to E-30 Bastianni. Conducting transepithelial electrical resistance (TEER), paracellular dextran flux measurement, quantitative real-time polymerase chain reaction (qPCR), western blot, and immunofluorescence analysis, we investigated TJ and AJ function and morphology as well as strain-specific E-30 infection patterns. Additionally, transmission electron and focused ion beam microscopy electron microscopy (FIB-SEM) was used to evaluate the mode of leukocyte transmigration. Genome sequencing and phylogenetic analyses were performed to discriminate potential genetic differences among the outbreak strains.    Results: We observed a significant strain-dependent decrease in TEER with strains E-30 Bastianni and 13-311, whereas paracellular dextran flux was only affected by E-30 Bastianni. Despite strong similarities among the outbreak strains in replication characteristics and particle distribution, strain 13-311 was the only outbreak isolate revealing comparable disruptive effects on TJ (Zonula Occludens (ZO) 1 and occludin) and AJ (E-cadherin) morphology to E-30 Bastianni. Notwithstanding significant junctional alterations upon E-30 infection, we observed both para- and transcellular leukocyte migration across HIBCPP cells. Complete genome sequencing revealed differences between the strains analyzed, but no explicit correlation with the observed strain-dependent effects on HIBCPP cells was possible.    Conclusion: The findings revealed distinct E-30 strain-specific effects on barrier integrity and junctional morphology. Despite E-30-induced barrier alterations leukocyte trafficking did not exclusively occur via the paracellular route.
publisher: BioMed Central
date: 2018
type: Article
type: info:eu-repo/semantics/article
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/24309/1/12974_2018_Article_1061.pdf
identifier: DOI:
identifier: urn:nbn:de:bsz:16-heidok-243096
identifier:   Dahm, Tobias ; Adams, Ortwin ; Boettcher, Sindy ; Diedrich, Sabine ; Morozov, Vasily ; Hansman, Grant ; Fallier-Becker, Petra ; Schädler, Sebastian ; Burkhardt, Claus J. ; Weiss, Christel ; Stump-Guthier, Carolin ; Ishikawa, Hiroshi ; Schroten, Horst ; Schwerk, Christian ; Tenenbaum, Tobias ; Rudolph, Henriette  (2018) Strain-dependent effects of clinical echovirus 30 outbreak isolates at the blood-CSF barrier.  Journal of Neuroinflammation, 15 (50).  pp. 1-19.  ISSN 1742-2094     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/24309/
rights: info:eu-repo/semantics/openAccess
rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id)
language: eng