Glycans and host-pathogen interactions

We have employed synthetic glycans to probe receptor specificities of various pathogenic viruses. It revealed that recent A/H3N2 influenza viruses have compensated for decreased binding of the prototypic human receptor by recognizing 2,6-sialosides on extended LacNAc moieties. Erythrocyte glycomics showed an absence of extended glycans, providing a rationale for lack of agglutination by recent A/H3N2 viruses. A glycan remodeling approach installed functional receptors on erythrocytes, allowing antigenic characterization of recent A/H3N2 viruses and confirming the cocirculation of several antigenically different viruses in humans. Employing synthetic glycan, mechanisms important for maintaining the balance in HA and NA activities were uncovered. Using an array of heparan sulfate (HS)-oligosaccharides, we demonstrated, for the first time, the receptor binding domain (RBD) of the spike of SARS-CoV-2 can bind HS in a length and sequence-dependent manner. In another study, we examined receptor specificities of human and animal viruses that engage with O-acetylated sialic acid, including betacoronaviruses, toroviruses, and influenza C and D viruses. Key to these studies was the development of a chemo-enzymatic methodology that can provide almost any sialate-acetylation pattern. A collection of O-acetylated sialoglycans was printed as a microarray for receptor specificity determination. These studies showed host-specific patterns of receptor recognition and revealed that three distinct human respiratory viruses uniquely bind 9-O-acetylated α2,8-linked disialoside. Immuno-fluorescence and cell entry studies support that such glycotope as part of a ganglioside is a functional receptor for human coronaviruses. 

Broszeit K, Beek RJ van, Unione L, Bestebroer TM, Chapla D., Yang JY, Moremen KW, Herfst S, Fouchier RAM, Vries RP de, Boons GJ (2021) Glycan remodeled erythrocytes facilitate antigenic characterization of recent A/H3N2 influenza viruses. Nat Commun In press. 

Liu L, Chopra P, Li X, Bouwman KM, Tompkins SM, Wolfert MA, Vries de RP, Boons GJ (2021) Heparan sulfate proteoglycans as attachment factor for SARS-CoV-2. ACS Cent Sci 7(6): 1009-1018. 

Li Z, Lang Y, Liu L, Bunyatov MI, Sarmiento AI, de Groot RJ, Boons GJ (2021) Synthetic O-Acetylated sialosides facilitate functional receptor identification for human respiratory viruses. Nat Chem 13(5): 496-503. 

Wang Z, Chinoy Z, Ambre S, Peng W, McBride R, de Vries RP, Glushka J, Paulson JC, Boons GJ (2013) A general strategy for the chemoenzymatic synthesis of asymmetrically branched N-glycans. Science 341(6144):379-383.