Overcoming the Barrier of the Respiratory Epithelium during Canine Distemper Virus Infection
Dai‐Lun Shin, Elisa Chludzinski, Nai‐Huei Wu, Ju-Yi Peng, Małgorzata Ciurkiewicz, Bevan Sawatsky, Christian K. Pfaller, Christine Baechlein, Veronika von Messling, Ludwig Haas, Andreas Beineke, Georg Herrler
Abstract
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.