In vitro infection with dengue virus induces changes in the structure and function of the mouse brain endothelium

dc.contributor.authorVelandia-Romero, Myriam Lucía
dc.contributor.authorCalderón-Peláez, María Angélica
dc.contributor.authorCastellanos, Jaime
dc.contributor.orcidCastellanos, Jaime [0000-0003-1596-8383]
dc.contributor.orcidVelandia-Romero, Myriam Lucía [0000-0002-3340-7304]
dc.date.accessioned2020-04-20T00:49:39Z
dc.date.available2020-04-20T00:49:39Z
dc.date.issued2015
dc.description.abstractenglishBackground The neurological manifestations of dengue disease are occurring with greater frequency, and currently, no information is available regarding the reasons for this phenomenon. Some viruses infect and/or alter the function of endothelial organs, which results in changes in cellular function, including permeability of the blood-brain barrier (BBB), which allows the entry of infected cells or free viral particles into the nervous system. Methods In the present study, we standardized two in vitro models, a polarized monolayer of mouse brain endothelial cells (MBECs) and an organized co-culture containing MBECs and astrocytes. Using these cell models, we assessed whether DENV-4 or the neuro-adapted dengue virus (D4MB-6) variant infects cells or induces changes in the structure or function of the endothelial barrier. Results The results showed that MBECs, but not astrocytes, were susceptible to infection with both viruses, although the percentage of infected cells was higher when the neuro-adapted virus variant was used. In both culture systems, DENV infection changed the localization of the tight junction proteins Zonula occludens (ZO-1) and Claudin-1 (Cln1), and this process was associated with a decrease in transendothelial resistance, an increase in macromolecule permeability and an increase in the paracellular passing of free virus particles. MBEC infection led to transcriptional up-regulation of adhesion molecules (VCAM-1 and PECAM) and immune mediators (MCP-1 and TNF- α) that are associated with immune cell transmigration, mainly in D4MB-6-infected cells. Conclusion These results indicate that DENV infection in MBECs altered the structure and function of the BBB and activated the endothelium, affecting its transcellular and paracellular permeability and favoring the passage of viruses and the transmigration of immune cells. This phenomenon can be harnessed for neurotropic and neurovirulent strains to infect and induce alterations in the CNS.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0157786
dc.identifier.instnameinstname:Universidad El Bosquespa
dc.identifier.issn1932-6203
dc.identifier.reponamereponame:Repositorio Institucional Universidad El Bosquespa
dc.identifier.repourlrepourl:https://repositorio.unbosque.edu.co
dc.identifier.urihttps://hdl.handle.net/20.500.12495/2302
dc.language.isospa
dc.publisherPublic Library of Sciencespa
dc.publisher.journalPlos onespa
dc.relation.ispartofseriesPlos one, 1932-6203. Vol, 10, Nro. 10, 2015spa
dc.relation.urihttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157786
dc.rightsAttribution 4.0 International*
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.accessrightshttps://purl.org/coar/access_right/c_abf340
dc.rights.creativecommons2015
dc.rights.localAcceso abiertospa
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.decsDenguespa
dc.subject.decsCélulas endotelialesspa
dc.subject.decsManifestaciones neurológicasspa
dc.titleIn vitro infection with dengue virus induces changes in the structure and function of the mouse brain endotheliumspa
dc.title.translatedIn vitro infection with dengue virus induces changes in the structure and function of the mouse brain endothelium
dc.typearticlespa
dc.type.hasversioninfo:eu-repo/semantics/publishedVersion
dc.type.localartículospa

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