Long-Term Culture of Distal Airway Epithelial Cells Allows Differentiation Towards Alveolar Epithelial Cells Suited for Influenza Virus Studies

Imai-Matsushima, Aki; Martin-Sancho, Laura; Karlas, Alexander; Imai, Seiichiro; Zoranovic, Tamara; Hocke, Andreas C.; Mollenkopf, Hans-Joachim; Berger, Hilmar; Meyer, Thomas F.

To assess the potential of this model for influenza A virus research, we infected human and chicken DAECs with different IAV strains that have either known or predicted receptor-binding specificities, based on published data. A/WSN/1933 (H1N1) was reported to have α2-6 sialic acid receptor binding preference, which is the linkage most abundantly expressed in the human upper respiratory tract [28] , A/England/ 195/2009 (H1N1pdm) is predicted to have preference for α2-6 sialic acid receptors but might also bind avian-like α2-3 linkages based on the reported binding preferences of another representative pandemic H1N1 2009 virus [29] , A/Panama/2007/1999 (H3N2) has been reported to have α2-6 sialic acid receptor binding [30] , A/Vietnam/1203/2004 (H5N1) has been reported to have α2-3 sialic acid receptor binding preference [31] , and A/Mallard/Germany/439/2004 (H3N2) is predicted to have α2-3 receptor binding [32] . The lab-adapted A/WSN/1933(H1N1), the seasonal A/Panama/2007/ 1999(H3N2) and the pandemic A/England/195/2009(H1N1pdm), generated as a triple reassortant of human, porcine and avian viruses, replicated better in chicken DAECs (Fig. 6A-C) . A/Mallard/Germany/439/ 2004(H3N2) exhibited low replication efficiency, especially in human DAECs (Fig. 6D) , while the highly pathogenic A/Vietnam/1203/2004 (H5N1) replicated equally well in both species (Fig. 6E) .