Unknown

Dataset Information

0

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


ABSTRACT: 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 ?2,3-linked Sias over ?2,6-linked Sias, which correlates with the differential distribution of ?2,3-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.

SUBMITTER: Li W 

PROVIDER: S-EPMC5635925 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Li Wentao W   Hulswit Ruben J G RJG   Widjaja Ivy I   Raj V Stalin VS   McBride Ryan R   Peng Wenjie W   Widagdo W W   Tortorici M Alejandra MA   van Dieren Brenda B   Lang Yifei Y   van Lent Jan W M JWM   Paulson James C JC   de Haan Cornelis A M CAM   de Groot Raoul J RJ   van Kuppeveld Frank J M FJM   Haagmans Bart L BL   Bosch Berend-Jan BJ  

Proceedings of the National Academy of Sciences of the United States of America 20170918 40


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 S1<sup>A</sup> through S1<sup>D</sup> Binding of MERS-CoV to the cell surface entry receptor dipeptidyl peptidase 4 (DPP4) occurs vi  ...[more]

Similar Datasets

2014-06-10 | E-GEOD-55023 | biostudies-arrayexpress
| S-EPMC6986839 | biostudies-literature
| S-EPMC8214665 | biostudies-literature
| S-EPMC3789674 | biostudies-literature
| PRJNA376858 | ENA
| PRJNA297569 | ENA
| PRJNA681679 | ENA
| PRJNA681678 | ENA
| PRJNA517346 | ENA
| PRJNA316178 | ENA