Journal Article

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

Raman, Rahul, Sasisekharan, Ram, Viswanathan, Karthik, Srinivasan, Karunya, Jayaraman, Akila

2013

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adaptation / Affinity / Avian flu / Avian influenza / Avian influenza viruses / Binding sites / Biological evolution / Biology / Conjunctivitis / Epidemics / Glycan / Health aspects / Hemagglutinin Glycoproteins, Influenza Virus - chemistry / Hemagglutinin Glycoproteins, Influenza Virus - metabolism / Hemagglutinins / Humans / Illnesses / Influenza / Influenza A / Influenza A virus - metabolism / Influenza A Virus, H7N2 Subtype - metabolism / Influenza A Virus, H7N7 Subtype - metabolism / Influenza, Human - pathology / Influenza, Human - virology / Lectins / Medicine / Mutant Proteins - metabolism / Mutation / Mutation - genetics / Pandemics / Polysaccharides / Protein Binding / Pulmonary Alveoli - pathology / Pulmonary Alveoli - virology / Receptors / Receptors, Virus - chemistry / Receptors, Virus - metabolism / Respiratory diseases / Strains (organisms) / Trachea - pathology / Trachea - virology / Viruses