Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein

Middle East respiratory syndrome coronavirus (MERS-CoV) targets the epithelial cells of the respiratory tract both in humans and in its natural host, the dromedary camel. Virion attachment to host cells is mediated by 20-nm-long homotrimers of spike envelope protein S. The N-terminal subunit of each S protomer, called S1, folds into four distinct domains designated S1A through S1D. Binding of MERS-CoV to the cell surface entry receptor dipeptidyl peptidase 4 (DPP4) occurs via S1B. We now demonstrate that in addition to DPP4, MERS-CoV binds to sialic acid (Sia). Initially demonstrated by hemagglutination assay with human erythrocytes and intact virus, MERS-CoV Sia-binding activity was assigned to S subdomain S1A. When multivalently displayed on nanoparticles, S1 or S1A bound to human erythrocytes and to human mucin in a strictly Sia-dependent fashion. Glycan array analysis revealed a preference for α2,3-linked Sias over α2,6-linked Sias, which correlates with the differential distribution of α2,3-linked Sias and the predominant sites of MERS-CoV replication in the upper and lower respiratory tracts of camels and humans, respectively. Binding is hampered by Sia modifications such as 5-N-glycolylation and (7,)9-O-acetylation. Depletion of cell surface Sia by neuraminidase treatment inhibited MERS-CoV entry of Calu-3 human airway cells, thus providing direct evidence that virus–Sia interactions may aid in virion attachment. The combined observations lead us to propose that high-specificity, low-affinity attachment of MERS-CoV to sialoglycans during the preattachment or early attachment phase may form another determinant governing the host range and tissue tropism of this zoonotic pathogen..

Medienart:

Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:114

Enthalten in:

Proceedings of the National Academy of Sciences of the United States of America - 114(2017), 40, Seite E8508-E8517

Sprache:

Englisch

Beteiligte Personen:

Li, Wentao [VerfasserIn]
Hulswit, Ruben J.G [Sonstige Person]
Widjaja, Ivy [Sonstige Person]
Raj, V.S [Sonstige Person]
McBride, Ryan [Sonstige Person]
Peng, Wenjie [Sonstige Person]
Widagdo, W [Sonstige Person]
Tortorici, M.A [Sonstige Person]
Dieren, van, Brenda [Sonstige Person]
Lang, Yifei [Sonstige Person]
Lent, van, Jan W.M [Sonstige Person]
Paulson, James C [Sonstige Person]
Haan, de, Cornelis A.M [Sonstige Person]
Groot, de, Raoul J [Sonstige Person]
Kuppeveld, Van, Frank J.M [Sonstige Person]
Haagmans, Bart L [Sonstige Person]
Bosch, Berend-Jan [Sonstige Person]

Links:

www.narcis.nl

Themen:

Attachment
MERS-CoV
Receptor
Sialic acid
Spike

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC1998538788