Kinetic analysis of paramyxovirus-sialoglycan receptor interactions reveals virion motility.

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. Author summary: Many viruses attach to host cells using glycan receptors. These receptors are, however, extremely abundant in mucus, while also not all glycans on the cell surface will act as functional receptors. To prevent getting stuck to decoy receptors such viruses often contain in addition to a receptor-binding protein also a receptor-destroying enzyme. Several paramyxoviruses contain a hemagglutinin-neuraminidase, which combines sialoglycan receptor-binding and -cleavage properties in a single catalytic site. Here, we applied biolayer interferometry (BLI) to study the kinetics of the interactions between several human and animal paramyxoviruses and sialoglycan receptors. With BLI we can monitor in real time the binding and release of viruses with glycan receptors coated on a sensor surface. We show that the dynamics of these interactions may differ dramatically between viruses when using the same receptors. Dynamic interactions allow virus particle motility on a receptor-coated surface driven by sialidase activity and thus escape from decoy receptors. We propose that different virus-receptor dynamics evolve upon adaptation to different host species and that the balance between receptor binding and cleavage is an important determinant of host species tropism. [ABSTRACT FROM AUTHOR]