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. 2012 Feb;22(2):174-80.
doi: 10.1093/glycob/cwr112. Epub 2011 Aug 16.

Receptor-binding specificity of the human parainfluenza virus type 1 hemagglutinin-neuraminidase glycoprotein

Irina V Alymova  1 , Allen Portner, Vasiliy P Mishin, Jonathan A McCullers, Pamela Freiden, Garry L Taylor
Affiliations

Receptor-binding specificity of the human parainfluenza virus type 1 hemagglutinin-neuraminidase glycoprotein

Irina V Alymova et al. Glycobiology. 2012 Feb.

Abstract

The hemagglutinin-neuraminidase (HN) glycoprotein is utilized by human parainfluenza viruses for binding to the host cell. By the use of glycan array assays, we demonstrate that, in addition to the first catalytic-binding site, the HN of human parainfluenza virus type 1 has a second site for binding covered by N-linked glycan. Our data suggest that attachment of the first site to sialic acid (SA)-linked receptors triggers exposure of the second site. We found that both sites bind to α2-3-linked SAs with a preference for a sialyl-Lewis(x) motif. Binding to α2-3-linked SAs with a sulfated sialyl-Lewis motif as well as to α2-8-linked SAs was unique for the second binding site. Neither site recognizes α2-6-linked oligosaccharides.

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Figures

Fig. 1.
Fig. 1.
Chemical structures of Neu5Ac2en and BCX 2798 compounds. Neu5Ac2en (2-deoxy-2,3-dehydro-N-acetyl neuraminic acid); BCX 2798 (4-azido-5-isobutyrylamino-2,3-didehydro-2,3,4,5-tetradeoxy-d-glycero-d-galacto-2-nonulopyranosic acid).
Fig. 2.
Fig. 2.
Schematic view of the hPIV-1 HN dimer. The hPIV-1 HN dimer is modeled on the hPIV-3 HN dimer structure as reported previously (Alymova et al. 2008). The two monomers are colored in green and cyan, and show the location of Sites 1 and 2. The approximate location of Asn173 is indicated. The N-linked oligosaccharide, shown as a black oval, occludes Site 2.
Fig. 3.
Fig. 3.
Glycan array analysis showing binding of the parent and the N173S mutant. The binding of virus to each glycan is displayed in RFU. The average from four replicates for each glycan is plotted with error bars indicating standard error of mean (SEM). The glycan numbers refer to those on version 3.2 of the printed array. Structures for glycan numbers: 44, Neu5Acα2-3(6OSO3)Galβ1-4GlcNAc; 207, Neu5Acα2-3(6OSO3)Galβ1-4(Fucα1-3)GlcNAc; 208, Neu5Acα2-3(GalNAcβ1-4)Galβ1-4GlcNAc; 209, Neu5Acα2-3(GalNAcβ1-4)Galβ1-4GlcNAc; 210, Neu5Acα2-3(GalNAcβ1-4)Galβ1-4Glc; 228, Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAcb1-3Galβ1-4(Fucα1-3)GlcNAcb1-3Galβ1-4(Fucα1-3)GlcNAc; 229, Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAc; 230, Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAc; 231, Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAcβ1-3Gal; 232, Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAcβ1-3Galβ1-4GlcNAc; 234, Neu5Acα2-3Galβ1-4GlcNAcβ1-3Galβ1-4GlcNAcβ1-3Galβ1-4GlcNAc; 282, Neu5Aα2-3Galβ1-4GlcNAcβ1-3Galb1-3GlcNAc; 251, Neu5Acα2-8Neu5Acα2-3-Galβ1-4Glc. Details for other glycans can be found at www.functionalglycomics.org.
Fig. 4.
Fig. 4.
Schematic presentation of hPIV-1 HN receptor-binding specificity.
See this image and copyright information in PMC

References

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