Quantitative Description of Glycan-Receptor Binding of Influenza A Virus H7 Hemagglutinin

Karunya Srinivasan,Karthik Viswanathan,Akila Jayaraman,Rahul Raman,Ram Sasisekharan,Earl G Brown

doi:10.1371/journal.pone.0049597

Abstract

In the context of recently emerged novel influenza strains through reassortment, avian influenza subtypes such as H5N1, H7N7, H7N2, H7N3 and H9N2 pose a constant threat in terms of their adaptation to the human host. Among these subtypes, it was recently demonstrated that mutations in H5 and H9 hemagglutinin (HA) in the context of lab-generated reassorted viruses conferred aerosol transmissibility in ferrets (a property shared by human adapted viruses). We previously demonstrated that the quantitative binding affinity of HA to α2→6 sialylated glycans (human receptors) is one of the important factors governing human adaptation of HA. Although the H7 subtype has infected humans causing varied clinical outcomes from mild conjunctivitis to severe respiratory illnesses, it is not clear where the HA of these subtypes stand in regard to human adaptation since its binding affinity to glycan receptors has not yet been quantified. In this study, we have quantitatively characterized the glycan receptor-binding specificity of HAs from representative strains of Eurasian (H7N7) and North American (H7N2) lineages that have caused human infection. Furthermore, we have demonstrated for the first time that two specific mutations; Gln226→Leu and Gly228→Ser in glycan receptor-binding site of H7 HA substantially increase its binding affinity to human receptor. Our findings contribute to a framework for monitoring the evolution of H7 HA to be able to adapt to human host.

Highlights

Avian influenza virus subtypes known to infect and cause disease in humans include H5N1, H7N7, H7N2, H7N3 and H9N2 strains
In this study we characterized in a quantitative fashion, the relative binding affinities of H7 HA to avian and human receptors given that some H7 strains especially from the Eurasian lineage are highly pathogenic and have caused human infections
The FC, CC and NY/107 strains were previously analyzed for their ability to transmit in the ferret animal model NY/107 and the highly pathogenic CC strain showed some transmission via direct contact, the other highly pathogenic strain isolated from fatal case did not show any transmission

Summary

Introduction

Avian influenza virus subtypes known to infect and cause disease in humans include H5N1, H7N7, H7N2, H7N3 and H9N2 strains. These viruses circulate in domestic poultry but have not yet adapted to the human host to establish sustained airborne human-to-human transmission capabilities [1]. In the past few years, novel influenza strains such as 2009 H1N1 and 2010 H3N2 that naturally emerged from multiple reassortment of viral gene segments between avian, swine and human isolates were able to successfully adapt to human host [4,5]. With the human population predominantly naıve to these avian influenza antigens, constant surveillance with particular focus on molecular changes geared towards human host adaptation becomes vital in this era of pandemics [6]

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Conclusion