Global aspects of viral glycosylation

Abstract

Enveloped viruses encompass some of the most common human pathogens causing infections of different severity, ranging from no or very few symptoms to lethal disease as seen with the viral hemorrhagic fevers. All enveloped viruses possess an envelope membrane derived from the host cell, modified with often heavily glycosylated virally encoded glycoproteins important for infectivity, viral particle formation and immune evasion. While N-linked glycosylation of viral envelope proteins is well characterized with respect to location, structure and site occupancy, information on mucin-type O-glycosylation of these proteins is less comprehensive. Studies on viral glycosylation are often limited to analysis of recombinant proteins that in most cases are produced in cell lines with a glycosylation capacity different from the capacity of the host cells. The glycosylation pattern of the produced recombinant glycoproteins might therefore be different from the pattern on native viral proteins. In this review, we provide a historical perspective on analysis of viral glycosylation, and summarize known roles of glycans in the biology of enveloped human viruses. In addition, we describe how to overcome the analytical limitations by using a global approach based on mass spectrometry to identify viral O-glycosylation in virus-infected cell lysates using the complex enveloped virus herpes simplex virus type 1 as a model. We underscore that glycans often pay important contributions to overall protein structure, function and immune recognition, and that glycans represent a crucial determinant for vaccine design. High throughput analysis of glycosylation on relevant glycoprotein formulations, as well as data compilation and sharing is therefore important to identify consensus glycosylation patterns for translational applications.

Glycoinformatics approach for identifying target positions to inhibit initial binding of SARS-CoV-2 S1 protein to the host cell

“…Since O-glycans are involved in proteinprotein interactions [19], we suggest that O-glycans at Thr323 may play a role on binding to ACE2 and O-glycans at Thr678, Thr686 may responsible for furin protease enzyme binding. It has been known that O-glycans are responsible for the protein stability and creating mucin like domain as glycan shields involved in immunoevasion [21]. Based on this, we suggest that the O-glycosylation positions found may be involved in the stability of the S1 protein and immunoevasion of virus to the host cell.…”

Deducing the N- and O- glycosylation profile of the spike protein of novel coronavirus SARS-CoV-2

“…O-glycans, which are involved in protein stability and function, have been observed on some viral proteins and have been suggested to play roles in the biological activity of viral proteins (Andersen, K.G., Rambaut, A., et al 2020, Bagdonaite, I. andWandall, H.H. 2018).…”

“…it is unclear what function these predicted O-linked glycans perform, they have been suggested to create a 'mucin-like domain' which could shield SARS-CoV-2 spike protein epitopes or key residues(Bagdonaite, I. and Wandall, H.H. 2018).…”

Glycosylation of viral surface proteins probed by mass spectrometry

“…Mass spectrometry in the analysis of viral surface protein glycosylation MS, the production and detection of ions separated according to their mass-to-charge (m/z) ratios, can provide structural identification of glycans, site-specific glycan characterization and be utilized to track changes in glycan composition, pattern, and site-occupancy [34][35][36]37 ]. Analysis of protein glycosylation by MS is typically achieved using two main approaches: glycans are released from the peptide backbone either enzymatically or chemically, or the glycoprotein can be subjected to protease digestion, producing a mixture of peptides and glycopeptides.…”