Three mutations switch H7N9 influenza to human-type receptor specificity.

Robert P De Vries,Ryan Mcbride,James C Paulson,Andrew J Thompson,Oliver C Grant,Ian A Wilson,Iresha N Ambepitiya Wickramasinghe,Alba T Torrents De La Pena,Robert J Woods,Wenli Yu,Xueyong Zhu,Kim M Bouwman,Monique H Verheije,Wenjie Peng,Marielle J Van Breemen,Cornelis A M De Haan,Rogier W Sanders

doi:10.1371/journal.ppat.1006390

Abstract

The avian H7N9 influenza outbreak in 2013 resulted from an unprecedented incidence of influenza transmission to humans from infected poultry. The majority of human H7N9 isolates contained a hemagglutinin (HA) mutation (Q226L) that has previously been associated with a switch in receptor specificity from avian-type (NeuAcα2-3Gal) to human-type (NeuAcα2-6Gal), as documented for the avian progenitors of the 1957 (H2N2) and 1968 (H3N2) human influenza pandemic viruses. While this raised concern that the H7N9 virus was adapting to humans, the mutation was not sufficient to switch the receptor specificity of H7N9, and has not resulted in sustained transmission in humans. To determine if the H7 HA was capable of acquiring human-type receptor specificity, we conducted mutation analyses. Remarkably, three amino acid mutations conferred a switch in specificity for human-type receptors that resembled the specificity of the 2009 human H1 pandemic virus, and promoted binding to human trachea epithelial cells.

Highlights

The 2013 avian H7N9 virus outbreak in China was tied to human exposure to infected poultry in live bird markets [1]
We show that recombinant H7 proteins
AJT is a recipient of a EMBO Long-term Fellowship (EMBO ALTF 963-2014)

Summary

Introduction

The 2013 avian H7N9 virus outbreak in China was tied to human exposure to infected poultry in live bird markets [1]. Receptor specificity of influenza A viruses is widely considered to be a barrier for transmission of avian influenza viruses in humans [6]. All human pandemic strains to date have exhibited specificity for human-type receptors (α2–6 linked), in contrast to their avian virus progenitors that recognize avian-type receptors (α2–3 linked) [7, 8]. The change in receptor specificity from avian-type to human-type involved two mutations in the HA receptor binding pocket, E190D and G225D for the H1N1 viruses, and Q226L and G228S for the H2N2 and H3N2 viruses [9, 10]

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Conclusion