Prior swine influenza virus infection of differentiated airway epithelial cells enhances secondary infection by avian influenza virus and facilitates the generation of reassortant viruses
Final Report Abstract
Pigs play an important role in the interspecies transmission of influenza A viruses (IAV). The porcine airway epithelium contains binding sites for both swine/human IAV (α2,6-linked sialic acids) and avian IAV (α2,3-linked sialic acids) and therefore is suited for adaptation of viruses from other species as suggested by the “mixing vessel theory”. In this project, we applied well-differentiated airway epithelial cells from different species to find out the possibility of co-infection of two IAVs could be initiated and affected by the sialic acid-binding preference of IAVs. Our result showed that, by using swine, human, and ferret air-liquid interface (ALI) cultures, the sialic acid-binding activity associated infectivity of the IAVs was not the sole factor for infecting another species. In addition, we found out at least one avian IAV H1N1 strain circulating in European poultry and waterfowl shows increased and prolonged viral replication in the swine ALI cultures without inducing a strong innate immune response. In the combination of applying the poly(I:C) and Ruxolitinib as the stimulator and inhibitor, respectively, for interferon-stimulated innate immune response, we were able to observe the different strategies of swine and avian IAVs to regulate Mx1 antiviral function in the ALI cultures which would be crucial for the concurrent co-infection of different IAVs. Aside from the IAVs, in the project, we also collaborated with other institutes for studying various viral diseases by using our established primary cell cultures. For instance, by using the primary human airway epithelial cells, we had achieved in identified a potential drug candidate "Camostat" to treat the COVID-19 in the very beginning of the crisis in 2020. In sum, the well-differentiated ALI cultures can mimic the environment for the airway epithelium, which followed the 3R principle could be an ideal model to study the respiratory diseases in more details.
Publications
- 2020. Avian Influenza A Virus Infects Swine Airway Epithelial Cells without Prior Adaptation. Viruses 12, 589
Shin, D.-L., Yang, W., Peng, J.-Y., Sawatsky, B., von Messling, V., Herrler, G., Wu, N.-H.
(See online at https://doi.org/10.3390/v12060589) - 2020. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 181, 271-280.e278
Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T.S., Herrler, G., Wu, N.H., Nitsche, A., Müller, M.A., Drosten, C., Pöhlmann, S.
(See online at https://doi.org/10.1016/j.cell.2020.02.052) - The cell tropism of porcine respiratory coronavirus for porcine airway epithelial cells is determined by the expression of the receptor pAPN and by the differentiation state of the cells. Viruses 12(11), 1211
Peng, J.Y., Punyadarsaniya, D., Shin, D.L., Pavasutthipaisit, S., Beineke, A., Li, G.X., Wu, N.H., Herrler, G.
(See online at https://doi.org/10.3390/v12111211)
