%0 Journal Article
%@ 1742-2094
%A Dahm, Tobias
%A Adams, Ortwin
%A Boettcher, Sindy
%A Diedrich, Sabine
%A Morozov, Vasily
%A Hansman, Grant
%A Fallier-Becker, Petra
%A Schädler, Sebastian
%A Burkhardt, Claus J.
%A Weiss, Christel
%A Stump-Guthier, Carolin
%A Ishikawa, Hiroshi
%A Schroten, Horst
%A Schwerk, Christian
%A Tenenbaum, Tobias
%A Rudolph, Henriette
%C London
%D 2018
%F heidok:24309
%I BioMed Central
%J Journal of Neuroinflammation
%N 50
%P 1-19
%T Strain-dependent effects of clinical echovirus 30 outbreak isolates at the blood-CSF barrier
%U https://archiv.ub.uni-heidelberg.de/volltextserver/24309/
%V 15
%X 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.