title: Japanese encephalitis virus disrupts cell-cell junctions and affects the epithelial permeability barrier functions.
abstract: Japanese encephalitis virus (JEV) is a neurotropic flavivirus, which causes viral encephalitis leading to death in about 20-30% of severely-infected people. Although JEV is known to be a neurotropic virus its replication in non-neuronal cells in peripheral tissues is likely to play a key role in viral dissemination and pathogenesis. We have investigated the effect of JEV infection on cellular junctions in a number of non-neuronal cells. We show that JEV affects the permeability barrier functions in polarized epithelial cells at later stages of infection. The levels of some of the tight and adherens junction proteins were reduced in epithelial and endothelial cells and also in hepatocytes. Despite the induction of antiviral response, barrier disruption was not mediated by secreted factors from the infected cells. Localization of tight junction protein claudin-1 was severely perturbed in JEV-infected cells and claudin-1 partially colocalized with JEV in intracellular compartments and targeted for lysosomal degradation. Expression of JEV-capsid alone significantly affected the permeability barrier functions in these cells. Our results suggest that JEV infection modulates cellular junctions in non-neuronal cells and compromises the permeability barrier of epithelial and endothelial cells which may play a role in viral dissemination in peripheral tissues.
authors.affiliation: Vaccine and Infectious Disease Research Center, Translational Health Science and Technology Institute, Gurgaon, India.
authors.forename: Tanvi
authors.initials: T
authors.lastname: Agrawal
authors.forename: Vats
authors.initials: V
authors.lastname: Sharvani
authors.forename: Deepa
authors.initials: D
authors.lastname: Nair
authors.forename: Guruprasad R
authors.initials: GR
authors.lastname: Medigeshi
mesh_terms: D015153:Blotting, Western; D018938:Caco-2 Cells; D002460:Cell Line; D062445:Claudin-1 / Q000378:metabolism; D004664:Encephalitis Virus, Japanese / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D005455:Fluorescent Antibody Technique; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000821:virology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014779:Virus Replication / Q000502:physiology
chemical_list: D062445:Claudin-1; D017382:Reactive Oxygen Species
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