title: Wild-type measles virus infection of primary epithelial cells occurs via the basolateral surface without syncytium formation or release of infectious virus.
abstract: The lymphotropic and myelotropic nature of wild-type measles virus (wt-MV) is well recognized, with dendritic cells and lymphocytes expressing the MV receptor CD150 mediating systemic spread of the virus. Infection of respiratory epithelial cells has long been considered crucial for entry of MV into the body. However, the lack of detectable CD150 on these cells raises the issue of their importance in the pathogenesis of measles. This study utilized a combination of in vitro, ex vivo and in vivo model systems to characterize the susceptibility of epithelial cells to wt-MV of proven pathogenicity. Low numbers of MV-infected epithelial cells in close proximity to underlying infected lymphocytes or myeloid cells suggested infection via the basolateral side of the epithelium in the macaque model. In primary cultures of human bronchial epithelial cells, foci of MV-infected cells were only observed following infection via the basolateral cell surface. The extent of infection in primary cells was enhanced both in vitro and in ex vivo cornea rim tissue by disrupting the integrity of the cells prior to the application of virus. This demonstrated that, whilst epithelial cells may not be the primary target cells for wt-MV, areas of epithelium in which tight junctions are disrupted can become infected using high m.o.i. The low numbers of MV-infected epithelial cells observed in vivo in conjunction with the absence of infectious virus release from infected primary cell cultures suggest that epithelial cells have a peripheral role in MV transmission.
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University of Belfast, Belfast BT9 7BL, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Ludlow
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Rennick
authors.forename: Severine
authors.initials: S
authors.lastname: Sarlang
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Skibinski
authors.forename: Stephen
authors.initials: S
authors.lastname: McQuaid
authors.forename: Tara
authors.initials: T
authors.lastname: Moore
authors.forename: Rik L
authors.initials: RL
authors.lastname: de Swart
authors.forename: W Paul
authors.initials: WP
authors.lastname: Duprex
mesh_terms: D000818:Animals; D001980:Bronchi / Q000821:virology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004847:Epithelial Cells / Q000821:virology; D015726:Giant Cells / Q000502:physiology*; D049452:Green Fluorescent Proteins; D006801:Humans; D008251:Macaca; D008459:Measles virus / Q000502:physiology*; D051916:Membrane Cofactor Protein / Q000502:physiology; D014709:Vero Cells; D053586:Virus Internalization; D057074:Virus Release
chemical_list: C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins