Strain-dependent effects of clinical echovirus 30 outbreak isolates at the blood-CSF barrier
dc.contributor.author | Dahm, Tobias | |
dc.contributor.author | Adams, Ortwin | |
dc.contributor.author | Boettcher, Sindy | |
dc.contributor.author | Diedrich, Sabine | |
dc.contributor.author | Morozov, Vasily | |
dc.contributor.author | Hansman, Grant | |
dc.contributor.author | Fallier-Becker, Petra | |
dc.contributor.author | Schädler, Sebastian | |
dc.contributor.author | Burkhardt, Claus J. | |
dc.contributor.author | Weiss, Christel | |
dc.contributor.author | Stump-Guthier, Carolin | |
dc.contributor.author | Ishikawa, Hiroshi | |
dc.contributor.author | Schroten, Horst | |
dc.contributor.author | Schwerk, Christian | |
dc.contributor.author | Tenenbaum, Tobias | |
dc.contributor.author | Rudolph, Henriette | |
dc.date.accessioned | 2018-05-07T21:10:39Z | |
dc.date.available | 2018-05-07T21:10:39Z | |
dc.date.created | 2018-03-07 | |
dc.date.issued | 2018-02-20 | none |
dc.identifier.other | http://edoc.rki.de/oa/articles/rem6FktdPHth6/PDF/278Hu7DODPaZ6.pdf | |
dc.identifier.uri | http://edoc.rki.de/176904/3012 | |
dc.description.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. | eng |
dc.language.iso | eng | |
dc.publisher | Robert Koch-Institut, Infektionskrankheiten / Erreger | |
dc.subject | Meningitis | eng |
dc.subject | CNS | eng |
dc.subject | Enterovirus | eng |
dc.subject | Echovirus (E-30) | eng |
dc.subject | Blood-cerebrospinal fluid barrier | eng |
dc.subject | Outbreak strains | eng |
dc.subject | Tight junction | eng |
dc.subject | Genomic sequencing | eng |
dc.subject | Transcellular transmigration | eng |
dc.subject | Paracellular transmigration | eng |
dc.subject.ddc | 610 Medizin | |
dc.title | Strain-dependent effects of clinical echovirus 30 outbreak isolates at the blood-CSF barrier | |
dc.type | periodicalPart | |
dc.identifier.urn | urn:nbn:de:0257-10058032 | |
dc.identifier.doi | 10.1186/s12974-018-1061-4 | |
dc.identifier.doi | http://dx.doi.org/10.25646/2937 | |
local.edoc.container-title | Journal of Neuroinflammation | |
local.edoc.fp-subtype | Artikel | |
local.edoc.type-name | Zeitschriftenartikel | |
local.edoc.container-type | periodical | |
local.edoc.container-type-name | Zeitschrift | |
local.edoc.container-url | https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-018-1061-4 | |
local.edoc.container-publisher-name | BioMedCentral | |
local.edoc.container-volume | 15 | |
local.edoc.container-issue | 50 | |
local.edoc.container-year | 2018 |