Abstract

An influenza H3N8 virus, carrying mammalian adaptation mutations, was isolated from New England harbor seals in 2011. We sought to assess the risk of its human transmissibility using two complementary approaches. First, we tested the binding of recombinant hemagglutinin (HA) proteins of seal H3N8 and human-adapted H3N2 viruses to respiratory tissues of humans and ferrets. For human tissues, we observed strong tendency of the seal H3 to bind to lung alveoli, which was in direct contrast to the human-adapted H3 that bound mainly to the trachea. This staining pattern was also consistent in ferrets, the primary animal model for human influenza pathogenesis. Second, we compared the binding of the recombinant HAs to a library of 610 glycans. In contrast to the human H3, which bound almost exclusively to α-2,6 sialylated glycans, the seal H3 bound preferentially to α-2,3 sialylated glycans. Additionally, the seal H3N8 virus replicated in human lung carcinoma cells. Our data suggest that the seal H3N8 virus has retained its avian-like receptor binding specificity, but could potentially establish infection in human lungs.

Highlights

  • Ferret respiratory tissues, and to chemically synthesized glycan arrays

  • In contrast to the human-adapted H3 control (A/Wyoming/03/2003), our findings suggest that the seal H3N8 HA preferentially binds to SAα -2,3Gal receptors that are abundant on human lungs[26]

  • We present evidence that seal H3N8 virus replicated in human lung carcinoma cells, highlighting the importance of continuous monitoring of influenza viruses circulating in seals for the early detection of strains with enhanced zoonotic potential

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Summary

Introduction

Ferret respiratory tissues, and to chemically synthesized glycan arrays. Seasonal human-adapted strains of influenza are known to bind to SAα -2,6Gal receptors[25], and are an epidemiologically relevant control for our study. In contrast to the human-adapted H3 control (A/Wyoming/03/2003), our findings suggest that the seal H3N8 HA preferentially binds to SAα -2,3Gal receptors that are abundant on human lungs[26]. We present evidence that seal H3N8 virus replicated in human lung carcinoma cells, highlighting the importance of continuous monitoring of influenza viruses circulating in seals for the early detection of strains with enhanced zoonotic potential

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