Abstract

Wild birds of Anseriformes and Charadriiformes are natural reservoirs of influenza A viruses (IAVs). Occasionally, IAVs transmit and adapt to mammalian hosts, and are maintained as epidemic strains in their new hosts. Viral adaptions to mammalian hosts include altered receptor preference of host epithelial sialylated oligosaccharides from terminal α2,3-linked sialic acid (SA) towards α2,6-linked SA. However, α2,3-linked SA has been found in human respiratory tract epithelium, and human infections by avian IAVs (AIVs) have been reported. To further explore the attachment properties of AIVs, four AIVs of different subtypes were investigated on human and pig tissues using virus histochemistry. Additionally, glycan array analysis was performed for further characterization of IAVs’ receptor structure tropism. Generally, AIV attachment was more abundant to human tissues than to pig tissues. The attachment pattern was very strong to human conjunctiva and upper respiratory tract, but variable to the lower respiratory tract. AIVs mainly attached to α2,3-linked SA, but also to combinations of α2,3- and α2,6-linked SA. The low attachment of these AIV isolates to pig tissues, but high attachment to human tissues, addresses the question whether AIVs in general require passage through pigs to obtain adaptions towards mammalian receptor structures.

Highlights

  • Global circulation of influenza A viruses (IAVs) in animals, especially avian IAVs (AIVs) in birds, poses a risk for development of IAVs pathogenic to humans[1]

  • IAV transmission dynamics is characterized by a high amount of different possible subtypes circulating in wild birds[1,2]

  • Reported human cases of low pathogenic AIVs (LPAIVs) and highly pathogenic AIVs (HPAIV) infections have repeatedly shown the possibility of direct IAV transmission between avian and human hosts[21,22], and it is of importance to investigate the zoonotic potential of AIVs

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Summary

Introduction

Global circulation of influenza A viruses (IAVs) in animals, especially avian IAVs (AIVs) in birds, poses a risk for development of IAVs pathogenic to humans[1]. In another study of mallard IAVs of various subtypes (H1, H2, H4 and H10), the highest viral affinity was observed for Neu5Acα2-3Galβ1-3GlcNAc (SLec)[13] These studies suggested that human IAVs have the highest observed affinity for 6′SLN, whereas AIVs have the highest affinity for 3′SLN or 3′STF with slight modifications depending on the avian host species[13,14,15]. The viral panel was assembled to include IAV of various subtypes and host origins to cover different functional and evolutionary differences in the IAV pool, and was analysed on human and pig respiratory tissues due to the nature of IAVs causing respiratory infections in these animals and reports of the pig respiratory tract being susceptible to both avian and human IAVs10. Human colon was included for comparison, since AIVs usually infect the gastrointestinal tract in most birds[1]

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