eprintid: 24309
rev_number: 14
eprint_status: archive
userid: 1589
dir: disk0/00/02/43/09
datestamp: 2018-04-25 12:24:18
lastmod: 2024-04-13 03:32:34
status_changed: 2018-04-25 12:24:18
type: article
metadata_visibility: show
creators_name: Dahm, Tobias
creators_name: Adams, Ortwin
creators_name: Boettcher, Sindy
creators_name: Diedrich, Sabine
creators_name: Morozov, Vasily
creators_name: Hansman, Grant
creators_name: Fallier-Becker, Petra
creators_name: Schädler, Sebastian
creators_name: Burkhardt, Claus J.
creators_name: Weiss, Christel
creators_name: Stump-Guthier, Carolin
creators_name: Ishikawa, Hiroshi
creators_name: Schroten, Horst
creators_name: Schwerk, Christian
creators_name: Tenenbaum, Tobias
creators_name: Rudolph, Henriette
title: Strain-dependent effects of clinical echovirus 30 outbreak isolates at the blood-CSF barrier
subjects: 570
subjects: 610
divisions: 62000
divisions: 911700
divisions: 911800
abstract: 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.
date: 2018
publisher: BioMed Central
id_scheme: DOI
ppn_swb: 165526950X
own_urn: urn:nbn:de:bsz:16-heidok-243096
language: eng
bibsort: DAHMTOBIASSTRAINDEPE2018
full_text_status: public
publication: Journal of Neuroinflammation
volume: 15
number: 50
place_of_pub: London
pagerange: 1-19
issn: 1742-2094
citation:   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     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/24309/1/12974_2018_Article_1061.pdf