title: Differential permissivity of human cerebrovascular endothelial cells to enterovirus infection and specificities of serotype EV-A71 in crossing an in vitro model of the human blood-brain barrier.
abstract: Human cerebral microvascular endothelial cells (hCMEC/D3 cell line) form a steady polarized barrier when cultured in vitro on a permeable membrane. Their susceptibility to enterovirus (EV) strains was analysed to investigate how these viruses may cross the blood-brain barrier. A sample of 88 virus strains was selected on phylogenetic features amongst 43 epidemiologically relevant types of the four EV species A-D. The EV-A71 genome was replicated at substantial rates, whilst the infectious virus was released at extremely low but sustained rates at both barrier sides for at least 4 days. EV-A71 antigens were detected in a limited number of cells. The properties of the endothelial barrier (structure and permeability) remained intact throughout infection. The chronic EV-A71 infection was in sharp contrast to the productive infection of cytolytic EVs (e.g. echoviruses E-6 and E-30). The hCMEC/D3 barriers infected with the latter EVs exhibited elevated proportions of apoptotic and necrotic cells, which resulted in major injuries to the endothelial barriers with a dramatic increase of paracellular permeability and virus crossing to the abluminal side. The following intracellular rearrangements were also seen: early destruction of the actin cytoskeleton, remodelling of intracellular membranes and reorganization of the mitochondrion network in a small cluster near the perinuclear space.
authors.affiliation: 1Clermont Université, Université d'Auvergne, EPIE, EA 4843, Clermont-Ferrand, France 2CHU Clermont-Ferrand, Service de Virologie, Clermont-Ferrand, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Volle
authors.affiliation: 1Clermont Université, Université d'Auvergne, EPIE, EA 4843, Clermont-Ferrand, France 2CHU Clermont-Ferrand, Service de Virologie, Clermont-Ferrand, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Archimbaud
authors.affiliation: 4Inserm, U1016, Institut Cochin, Paris, France.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Couraud
authors.affiliation: 5Department of Life, Health and Chemical Sciences, Open University, Milton Keynes, UK.
authors.forename: Ignacio A
authors.initials: IA
authors.lastname: Romero
authors.affiliation: 6Weill Cornell Medical College, New York, NY, USA.
authors.forename: Babette
authors.initials: B
authors.lastname: Weksler
authors.affiliation: 1Clermont Université, Université d'Auvergne, EPIE, EA 4843, Clermont-Ferrand, France 2CHU Clermont-Ferrand, Service de Virologie, Clermont-Ferrand, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Mirand
authors.affiliation: 3CHU Clermont-Ferrand, DRCI, Clermont-Ferrand, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pereira
authors.affiliation: 2CHU Clermont-Ferrand, Service de Virologie, Clermont-Ferrand, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Henquell
authors.affiliation: 1Clermont Université, Université d'Auvergne, EPIE, EA 4843, Clermont-Ferrand, France 2CHU Clermont-Ferrand, Service de Virologie, Clermont-Ferrand, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Peigue-Lafeuille
authors.affiliation: 1Clermont Université, Université d'Auvergne, EPIE, EA 4843, Clermont-Ferrand, France 2CHU Clermont-Ferrand, Service de Virologie, Clermont-Ferrand, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Bailly
mesh_terms: D000956:Antigens, Viral / Q000032:analysis; D017209:Apoptosis; D001812:Blood-Brain Barrier / Q000821:virology*; D002460:Cell Line; D042783:Endothelial Cells / Q000502:physiology* / Q000821:virology*; D004770:Enterovirus / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D010539:Permeability; D065288:Serogroup
chemical_list: D000956:Antigens, Viral