Avian Influenza A Virus Infects Swine Airway Epithelial Cells without Prior Adaptation

Bevan Sawatsky,Wei Yang,Dai-Lun Shin,Georg Herrler,Veronika von Messling,Nai-Huei Wu,Ju-Yi Peng

doi:10.3390/v12060589

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”. Here, we applied well-differentiated swine airway epithelial cells to find out whether efficient infection by avian IAV requires prior adaption. Furthermore, we analyzed the influence of the sialic acid-binding activity and the virus-induced detrimental effects. Surprisingly, an avian IAV H1N1 strain circulating in European poultry and waterfowl shows increased and prolonged viral replication without inducing a strong innate immune response. This virus could infect the lower respiratory tract in our precision cut-lung slice model. Pretreating the cells with poly (I:C) and/or JAK/STAT pathway inhibitors revealed that the interferon-stimulated innate immune response influences the replication of avian IAV in swine airway epitheliums but not that of swine IAV. Further studies indicated that in the infection by IAVs, the binding affinity of sialic acid is not the sole factor affecting the virus infectivity for swine or human airway epithelial cells, whereas it may be crucial in well-differentiated ferret tracheal epithelial cells. Taken together, our results suggest that the role of pigs being the vessel of interspecies transmission should be reconsidered, and the potential of avian H1N1 viruses to infect mammals needs to be characterized in more detail.

Highlights

Influenza continues to be a serious health threat for humans and animals [1,2]
The classical swine influenza A viruses (IAV) (H1N1) that was circulating in North America originally adapted from the human IAV
Primary swine airway epithelial cells were infected by avian IAVs of different subtypes or swine

Summary

Introduction

Influenza continues to be a serious health threat for humans and animals [1,2]. The swine-origin influenza A (H1N1) virus caused a pandemic in 2009, while the outbreak of highly pathogenic avian influenza (H5N1) viruses and the emerging H7N9 and H10N8 low pathogenic avian influenza viruses continue to cause human death until now [3,4,5]. While avian influenza A viruses (IAVs) have the ability to infect different mammalian. Analyses of the sialic acid-binding activity in the 1980s have revealed that human IAVs preferentially use α2,6-linked sialic acid as a receptor determinant for attachment to host cells when initiating an infection [11]. Avian viruses were found to preferentially recognize α2,3-linked sialic acids. The relationship between avian IAVs and influenza A viruses that are circulating in swine populations (swine IAV) worldwide is rather complicated [15]. Swine IAVs may contain RNA segments of both human and avian origin via adaptation and reassortment. The classical swine IAV (H1N1) that was circulating in North America originally adapted from the human IAV.

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Conclusion