Paramyxovirus infection driven by heteromultivalent sialoglycotope binding
Abstract
Sialic acids (Sia) on glycoproteins and glycosphingolipids act as receptors for many respiratory viruses, including human influenza A viruses and respiroviruses, which typically bind to α2-6- and α2-3-linked Sia (2-6Sia and 2-3Sia), respectively. In view of this binding discrepancy and as the exact sialoglycoconjugates supporting respirovirus infection remain unclear, we assessed the receptor requirements for infection and binding of several respiroviruses and avian Newcastle disease virus (NDV). To this end, we employed a library of isogenic HEK293 cells displaying defined sialoglycoconjugates. Respirovirus infection was shown to strictly depend on 2-3Sia, with a preference for the terminal Siaα2-3Galβ1-4GlcNAc sialoglycotope regardless of the underlying glycoconjugate structure, whereas NDV showed a broader sialoglycotope usage. Notably, 2-6Sia enhanced respirovirus infection in low 2-3Sia contexts via heteromultivalent surface binding, which resulted in prolonged virus–receptor interactions. This heteromultivalent binding is expected to aid respirovirus infection of the 2-6Sia-rich human upper respiratory tract.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (15)
Xuesheng Wu
Section Virology, Division Infectious Diseases and Immunology, Department Biomolecular Health Sciences, Faculty Veterinary Medicine, Utrecht University
Mengying Liu
Laura Blekkenhorst
Section Virology, Division Infectious Diseases and Immunology, Department Biomolecular Health Sciences, Faculty Veterinary Medicine, Utrecht University
Mare H. L. Verbruggen
Section Virology, Division Infectious Diseases and Immunology, Department Biomolecular Health Sciences, Faculty Veterinary Medicine, Utrecht University
Nancy N. M. P. Schuurman
Section Virology, Division Infectious Diseases and Immunology, Department Biomolecular Health Sciences, Faculty Veterinary Medicine, Utrecht University
Lemeng Chao
Department Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University
Jun Yang Ong
Department Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University
Tom Wennekes
Department Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University
Laura L. A. van Dijk
Department of Viroscience, Erasmus University Medical Center
Rory D. de Vries
Department of Viroscience, Erasmus University Medical Center
Frank J. M. van Kuppeveld
Henrik Clausen
Yoshiki Narimatsu
Erik de Vries
Cornelis A. M. de Haan
Section Virology, Division Infectious Diseases and Immunology, Department Biomolecular Health Sciences, Faculty Veterinary Medicine, Utrecht University