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1000 Titel
  • Overcoming the Barrier of the Respiratory Epithelium during Canine Distemper Virus Infection
1000 Autor/in
  1. Shin, Dai-Lun |
  2. Chludzinski, Elisa |
  3. Wu, Nai-Huei |
  4. Peng, Ju-Yi |
  5. Ciurkiewicz, Malgorzata |
  6. Sawatsky, Bevan |
  7. Pfaller, Christian |
  8. Baechlein, Christine |
  9. von Messling, Veronika |
  10. Haas, Ludwig |
  11. Beineke, Andreas |
  12. Herrler, Georg |
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2022-01-18
1000 Erschienen in
1000 Quellenangabe
  • 13(1):e03043-21
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2022
1000 Lizenz
1000 Verlagsversion
  • |
  • |
1000 Ergänzendes Material
  • |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Canine distemper virus (CDV) is a highly contagious pathogen and is known to enter the host via the respiratory tract and disseminate to various organs. Current hypotheses speculate that CDV uses the homologous cellular receptors of measles virus (MeV), SLAM and nectin-4, to initiate the infection process. For validation, here, we established the well-differentiated air-liquid interface (ALI) culture model from primary canine tracheal airway epithelial cells. By applying the green fluorescent protein (GFP)-expressing CDV vaccine strain and recombinant wild-type viruses, we show that cell-free virus infects the airway epithelium mainly via the paracellular route and only after prior disruption of tight junctions by pretreatment with EGTA; this infection was related to nectin-4 but not to SLAM. Remarkably, when CDV-preinfected DH82 cells were cocultured on the basolateral side of canine ALI cultures grown on filter supports with a 1.0-μm pore size, cell-associated CDV could be transmitted via cell-to-cell contact from immunocytes to airway epithelial cultures. Finally, we observed that canine ALI cultures formed syncytia and started to release cell-free infectious viral particles from the apical surface following treatment with an inhibitor of the JAK/STAT signaling pathway (ruxolitinib). Our findings show that CDV can overcome the epithelial barrier through different strategies, including infection via immunocyte-mediated transmission and direct infection via the paracellular route when tight junctions are disrupted. Our established model can be adapted to other animals for studying the transmission routes and the pathogenicity of other morbilliviruses. IMPORTANCE: Canine distemper virus (CDV) is not only an important pathogen of carnivores, but it also serves as a model virus for analyzing measles virus pathogenesis. To get a better picture of the different stages of infection, we used air-liquid interface cultures to analyze the infection of well-differentiated airway epithelial cells by CDV. Applying a coculture approach with DH82 cells, we demonstrated that cell-mediated infection from the basolateral side of well-differentiated epithelial cells is more efficient than infection via cell-free virus. In fact, free virus was unable to infect intact polarized cells. When tight junctions were interrupted by treatment with EGTA, cells became susceptible to infection, with nectin-4 serving as a receptor. Another interesting feature of CDV infection is that infection of well-differentiated airway epithelial cells does not result in virus egress. Cell-free virions are released from the cells only in the presence of an inhibitor of the JAK/STAT signaling pathway. Our results provide new insights into how CDV can overcome the barrier of the airway epithelium and reveal similarities and some dissimilarities compared to measles virus.
1000 Sacherschließung
lokal Staupe
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
1000 (Academic) Editor
1000 Label
1000 Förderer
  1. Deutsche Forschungsgemeinschaft |
1000 Fördernummer
  1. BE 4200/4-1; HA 1729/2-1; HE 1168/21-1
1000 Förderprogramm
  1. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer BE 4200/4-1; HA 1729/2-1; HE 1168/21-1
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6431718.rdf
1000 Erstellt am 2022-02-21T11:04:45.787+0100
1000 Erstellt von 323
1000 beschreibt frl:6431718
1000 Bearbeitet von 25
1000 Zuletzt bearbeitet Fri Mar 04 14:30:57 CET 2022
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