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2014-05-12Zeitschriftenartikel DOI: 10.1371/journal.pone.0096957
Tick-Borne Encephalitis Virus Replication, Intracellular Trafficking, and Pathogenicity in Human Intestinal Caco-2 Cell Monolayers
dc.contributor.authorYu, Chao
dc.contributor.authorAchazi, Katharina
dc.contributor.authorMöller, Lars
dc.contributor.authorSchulzke, Jörg D.
dc.contributor.authorNiedrig, Matthias
dc.contributor.authorBücker, Roland
dc.date.accessioned2018-05-07T17:41:25Z
dc.date.available2018-05-07T17:41:25Z
dc.date.created2014-05-27
dc.date.issued2014-05-12none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/rerJraduncFMY/PDF/25t4GYPAM2ExE.pdf
dc.identifier.urihttp://edoc.rki.de/176904/1883
dc.description.abstractTick-borne encephalitis virus (TBEV) is one of the most important vector-borne viruses in Europe and Asia. Its transmission mainly occurs by the bite of an infected tick. However, consuming milk products from infected livestock animals caused TBEV cases. To better understand TBEV transmission via the alimentary route, we studied viral infection of human intestinal epithelial cells. Caco-2 cells were used to investigate pathological effects of TBEV infection. TBEV-infected Caco-2 monolayers showed morphological changes including cytoskeleton rearrangements and cytoplasmic vacuolization. Ultrastructural analysis revealed dilatation of the rough endoplasmic reticulum and further enlargement to TBEV containing caverns. Caco-2 monolayers maintained an intact epithelial barrier with stable transepithelial electrical resistance (TER) during early stage of infection. Concomitantly, viruses were detected in the basolateral medium, implying a transcytosis pathway. When Caco-2 cells were pre-treated with inhibitors of cellular pathways of endocytosis TBEV cell entry was efficiently blocked, suggesting that actin filaments (Cytochalasin) and microtubules (Nocodazole) are important for PI3K-dependent (LY294002) virus endocytosis. Moreover, experimental fluid uptake assay showed increased intracellular accumulation of FITC-dextran containing vesicles. Immunofluorescence microscopy revealed co-localization of TBEV with early endosome antigen-1 (EEA1) as well as with sorting nexin-5 (SNX5), pointing to macropinocytosis as trafficking mechanism. In the late phase of infection, further evidence was found for translocation of virus via the paracellular pathway. Five days after infection TER was slightly decreased. Epithelial barrier integrity was impaired due to increased epithelial apoptosis, leading to passive viral translocation. These findings illuminate pathomechanisms in TBEV infection of human intestinal epithelial cells and viral transmission via the alimentary route.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut, Biologische Sicherheit
dc.subjectHumanseng
dc.subjectVirus Replicationeng
dc.subjectVirulenceeng
dc.subjectBiological Transporteng
dc.subjectCaco-2 Cellseng
dc.subjectCytoskeleton/virologyeng
dc.subjectEncephalitis Viruses Tick-Borne/metabolismeng
dc.subjectEncephalitis Viruses Tick-Borne/pathogenicityeng
dc.subjectEncephalitis Viruses Tick-Borne/physiologyeng
dc.subjectIntestines/cytologyeng
dc.subjectIntestines/ultrastructureeng
dc.subjectIntestines/virologyeng
dc.subjectIntracellular Space/virologyeng
dc.subjectPinocytosiseng
dc.subjectVirus Internalizationeng
dc.subject.ddc610 Medizin
dc.titleTick-Borne Encephalitis Virus Replication, Intracellular Trafficking, and Pathogenicity in Human Intestinal Caco-2 Cell Monolayers
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10036699
dc.identifier.doi10.1371/journal.pone.0096957
dc.identifier.doihttp://dx.doi.org/10.25646/1808
local.edoc.container-titlePLoS ONE
local.edoc.container-textYu C, Achazi K, Möller L, Schulzke JD, Niedrig M, et al. (2014) Tick-Borne Encephalitis Virus Replication, Intracellular Trafficking, and Pathogenicity in Human Intestinal Caco-2 Cell Monolayers. PLoS ONE 9(5): e96957.
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0096957
local.edoc.container-publisher-namePublic Library of Science
local.edoc.container-volume9
local.edoc.container-issue5
local.edoc.container-year2014

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