Kinetic analysis of paramyxovirus-sialoglycan receptor interactions reveals virion motility

Xuesheng Wu, Maite Goebbels, Lemeng Chao, Tom Wennekes, Frank J M van Kuppeveld, Erik de Vries, Cornelis A M de Haan*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Many viruses initiate infection by binding to sialoglycan receptors at the cell surface. Binding to such receptors comes at a cost, however, as the sheer abundance of sialoglycans e.g. in mucus, may immobilize virions to non-functional decoy receptors. As a solution, sialoglycan-binding as well as sialoglycan-cleavage activities are often present in these viruses, which for paramyxoviruses are combined in the hemagglutinin-neuraminidase (HN) protein. The dynamic interactions of sialoglycan-binding paramyxoviruses with their receptors are thought to be key determinants of species tropism, replication and pathogenesis. Here we used biolayer interferometry to perform kinetic analyses of receptor interactions of animal and human paramyxoviruses (Newcastle disease virus, Sendai virus, and human parainfluenza virus 3). We show that these viruses display strikingly different receptor interaction dynamics, which correlated with their receptor-binding and -cleavage activities and the presence of a second sialic acid binding site. Virion binding was followed by sialidase-driven release, during which virions cleaved sialoglycans until a virus-specific density was reached, which was largely independent of virion concentration. Sialidase-driven virion release was furthermore shown to be a cooperative process and to be affected by pH. We propose that paramyxoviruses display sialidase-driven virion motility on a receptor-coated surface, until a threshold receptor density is reached at which virions start to dissociate. Similar motility has previously been observed for influenza viruses and is likely to also apply to sialoglycan-interacting embecoviruses. Analysis of the balance between receptor-binding and -cleavage increases our understanding of host species tropism determinants and zoonotic potential of viruses.

Original languageEnglish
Article numbere1011273
Number of pages21
JournalPLoS Pathogens
Volume19
Issue number3
Early online date27 Mar 2023
DOIs
Publication statusPublished - Mar 2023

Bibliographical note

Publisher Copyright:
© 2023 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding

X.W. was supported by a personal grant from the Chinese Scholarship Council (202006010036). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

FundersFunder number
China Scholarship Council202006010036

    Keywords

    • Binding-site
    • Tropism
    • Human parainfluenza virus
    • Sialic-acid linkages
    • Specificity
    • Sendai virus
    • Cellular receptors
    • Newcastle-disease virus
    • Influenza-a
    • Hemagglutinin-neuraminidase protein

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