Biophysical Measurement of the Balance of Influenza A Hemagglutinin and Neuraminidase Activities

The interaction of influenza A viruses with the cell surface is controlled by the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). These two glycoproteins have opposing activities: HA is responsible for binding the host receptor (sialic acid) to allow infection, and NA is responsible...

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Bibliographic Details
Published in:The Journal of biological chemistry 2015-03, Vol.290 (10), p.6516-6521
Main Authors: Benton, Donald J., Martin, Stephen R., Wharton, Stephen A., McCauley, John W.
Format: Article
Language:English
Subjects:
Biophysical Phenomena
Biophysics
Enzyme Turnover
Hemagglutinin
Hemagglutinin Glycoproteins, Influenza Virus - chemistry
Hemagglutinin Glycoproteins, Influenza Virus - genetics
Hemagglutinin Glycoproteins, Influenza Virus - metabolism
Humans
Influenza A virus - chemistry
Influenza A virus - pathogenicity
Influenza Virus
Influenza, Human - genetics
Influenza, Human - pathology
Influenza, Human - virology
Kinetics
Microbiology
N-Acetylneuraminic Acid - chemistry
N-Acetylneuraminic Acid - genetics
Neuraminidase
Neuraminidase - chemistry
Neuraminidase - genetics
Protein Binding
Receptor Analogs
Receptor Binding
Receptors, Virus - chemistry
Receptors, Virus - metabolism
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Summary:The interaction of influenza A viruses with the cell surface is controlled by the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). These two glycoproteins have opposing activities: HA is responsible for binding the host receptor (sialic acid) to allow infection, and NA is responsible for cleaving the receptor to facilitate virus release. Several studies have demonstrated that compatible levels of HA and NA activity are required for a virus to replicate efficiently. This is consequently of great interest for determining virus transmissibility. The concurrent role of these two proteins in receptor binding has never been directly measured. We demonstrate a novel biophysical approach based on bio-layer interferometry to measure the balance of the activities of these two proteins in real time. This technique measures virus binding to and release from a surface coated with either the human-like receptor analog α2,6-linked sialic acid or the avian-like receptor analog α2,3-linked sialic acid in both the presence and absence of NA inhibitors. Bio-layer interferometry measurements were also carried out to determine the effect of altering HA receptor affinity and NA stalk length on receptor binding. Background: Influenza A viruses contain the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA), responsible for receptor binding and virus release, respectively. Results: The contribution of HA and NA to virus interactions with receptor-coated surfaces was measured using bio-layer interferometry. Conclusion: The balance between the activities of the two glycoproteins controls virus-cell interactions, therefore transmissibility. Significance: This technique can be used to examine factors underlying emergent virus transmissibility.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M114.622308