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Strain-dependent effects of clinical echovirus 30 outbreak isolates at the blood-CSF barrier

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

In: Journal of Neuroinflammation, 15 (2018), Nr. 50. pp. 1-19. ISSN 1742-2094

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Download (11MB) | Lizenz: Creative Commons LizenzvertragStrain-dependent effects of clinical echovirus 30 outbreak isolates at the blood-CSF barrier by 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 underlies the terms of Creative Commons Attribution 4.0

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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.

Item Type: Article
Journal or Publication Title: Journal of Neuroinflammation
Volume: 15
Number: 50
Publisher: BioMed Central
Place of Publication: London
Date Deposited: 25 Apr 2018 12:24
Date: 2018
ISSN: 1742-2094
Page Range: pp. 1-19
Faculties / Institutes: Medizinische Fakultät Mannheim > Kinderklinik
Medizinische Fakultät Heidelberg > Department for Infectiology
Medizinische Fakultät Heidelberg > Institut für Medizinische Biometrie und Informatik
Subjects: 570 Life sciences
610 Medical sciences Medicine
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