A differentiated porcine bronchial epithelial cell culture model for studying human adenovirus tropism and virulence

The species specificity of human adenoviruses (HAdV) almost precludes studying virulence and tropism in animal models, e.g. rodent models, or derived tissue and cell culture models. However, replication of HAdV type 5 (HAdV-C5) has been shown after intravenous injection in swine. In order to study adenovirus replication in airway tissue propagation of bronchial epithelial cells from porcine lungs was established. These primary cells proved to be fully permissive for HAdV-C5 infection in submerged culture, demonstrating efficient HAdV genome replication, infectious viral particle release (1.07 × 108 TCID50/ml ± 6.63 × 107) and development of cytopathic effect (CPE). Differentiation of porcine bronchial epithelial cells was achieved at the air-liquid interface on collagen I coated 0.4 μm polyester membranes. Morphology, expression of tubulin and occludin, the development of tight-junctions and cilia were similar to human bronchial epithelial cells. Infection with HAdV-C5 from the basolateral side resulted in release of infectious virus progeny (2.05 × 107 TCID50/ml ± 2.39 × 107) to the apical surface as described recently in human bronchial epithelial cells, although complete CPE was not observed. Differentiated porcine bronchial epithelial cells hold promise as a novel method for studying the virulence and pathophysiology of pneumonia associated HAdV types.

► Human adenovirus can cause severe lower airway infections. ► Species specificity of human adenovirus precludes the use of rodent models. ► Differentiated (polarized) porcine bronchial epithelial cells are permissive for human adenovirus infections. ► Differentiated porcine bronchial epithelial cells may substitute human bronchial epithelial cells which are difficult to obtain.