Canine Distemper Virus Alters Defense Responses in an Ex Vivo Model of Pulmonary Infection

犬瘟热病毒改变体外肺部感染模型中的防御反应

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作者:Elisa Chludzinski, Małgorzata Ciurkiewicz, Melanie Stoff, Johanna Klemens, Johannes Krüger, Dai-Lun Shin, Georg Herrler, Andreas Beineke

Abstract

Canine distemper virus (CDV), belonging to the genus Morbillivirus, is a highly contagious pathogen. It is infectious in a wide range of host species, including domestic and wildlife carnivores, and causes severe systemic disease with involvement of the respiratory tract. In the present study, canine precision-cut lung slices (PCLSs) were infected with CDV (strain R252) to investigate temporospatial viral loads, cell tropism, ciliary activity, and local immune responses during early infection ex vivo. Progressive viral replication was observed during the infection period in histiocytic and, to a lesser extent, epithelial cells. CDV-infected cells were predominantly located within the bronchial subepithelial tissue. Ciliary activity was reduced in CDV-infected PCLSs, while viability remained unchanged when compared to controls. MHC-II expression was increased in the bronchial epithelium on day three postinfection. Elevated levels of anti-inflammatory cytokines (interleukin-10 and transforming growth factor-β) were observed in CDV-infected PCLSs on day one postinfection. In conclusion, the present study demonstrates that PCLSs are permissive for CDV. The model reveals an impaired ciliary function and an anti-inflammatory cytokine response, potentially fostering viral replication in the lung during the early phase of canine distemper.

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