title: The differentiated airway epithelium infected by influenza viruses maintains the barrier function despite a dramatic loss of ciliated cells.
abstract: Virus-host interactions in the respiratory epithelium during long term influenza virus infection are not well characterized. Therefore, we developed an air-liquid interface culture system for differentiated porcine respiratory epithelial cells to study the effect of virus-induced cellular damage. In our well-differentiated cells, α2,6-linked sialic acid is predominantly expressed on the apical surface and the basal cells mainly express α2,3-linked sialic acid. During the whole infection period, release of infectious virus was maintained at a high titre for more than seven days. The infected epithelial cells were subject to apoptosis resulting in the loss of ciliated cells together with a thinner thickness. Nevertheless, the airway epithelium maintained trans-epithelial electrical resistance and retained its barrier function. The loss of ciliated cells was compensated by the cells which contained the KRT5 basal cell marker but were not yet differentiated into ciliated cells. These specialized cells showed an increase of α2,3-linked sialic acid on the apical surface. In sum, our results help to explain the localized infection of the airway epithelium by influenza viruses. The impairment of mucociliary clearance in the epithelial cells provides an explanation why prior viral infection renders the host more susceptible to secondary co-infection by another pathogen.
authors.affiliation: Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Nai-Huei
authors.initials: NH
authors.lastname: Wu
authors.affiliation: Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Institute of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Beineke
authors.affiliation: Federal Department of Home Affairs, Institute of Virology and Immunology, Bern, Switzerland.|Department of Infectious diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Switzerland.
authors.forename: Ronald
authors.initials: R
authors.lastname: Dijkman
authors.affiliation: Institute of Virology, Philipps University, Marburg, Germany.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Matrosovich
authors.affiliation: Institute of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumgärtner
authors.affiliation: Federal Department of Home Affairs, Institute of Virology and Immunology, Bern, Switzerland.|Department of Infectious diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Switzerland.
authors.forename: Volker
authors.initials: V
authors.lastname: Thiel
authors.affiliation: Institute for Microbiology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Valentin-Weigand
authors.affiliation: Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Fandan
authors.initials: F
authors.lastname: Meng
authors.affiliation: Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Herrler
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002923:Cilia / Q000378:metabolism*; D017097:Electric Impedance; D004847:Epithelial Cells / Q000276:immunology* / Q000821:virology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism; D009980:Influenza A virus / Q000502:physiology; D007700:Kinetics; D037102:Lectins / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011991:Receptors, Virus / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology* / Q000821:virology; D013552:Swine; D014132:Trachea / Q000378:metabolism; D014779:Virus Replication
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D037102:Lectins; D011991:Receptors, Virus; D019158:N-Acetylneuraminic Acid