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Molecules 2015, 20(3), 4610-4622; doi:10.3390/molecules20034610

Targeting N-Glycan Cryptic Sugar Moieties for Broad-Spectrum Virus Neutralization: Progress in Identifying Conserved Molecular Targets in Viruses of Distinct Phylogenetic Origins

1
Tumor Glycomics Laboratory, SRI International Biosciences Division, Menlo Park, CA 94025, USA
2
Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China
3
Instituteof Human Virology, Department of Biochemistry & Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
4
Department of Chemistry and Biochemistry, University of Maryland at College Park, College Park, MD 20742, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Vito Ferro and Trinidad Velasco-Torrijos
Received: 20 January 2015 / Revised: 26 February 2015 / Accepted: 9 March 2015 / Published: 12 March 2015
(This article belongs to the Collection Advances in Carbohydrate Chemistry)
View Full-Text   |   Download PDF [3624 KB, uploaded 12 March 2015]   |  

Abstract

Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA), for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific; the latter is broadly reactive and is able to neutralize viruses of distinct phylogenetic origins, such as HIV-1, severe acute respiratory syndrome coronavirus (SARS-CoV), and human cytomegalovirus (HCMV). In carbohydrate microarray analyses, we explored the molecular basis underlying the striking differences in the spectrum of anti-virus activities of the two probes. Unlike 2G12, which is strictly specific for the high-density Man9GlcNAc2Asn (Man9)-clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These include not only the known oligomannosyl antigens but also previously unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes (Tri/m-Gn). These findings highlight the potential of N-glycan cryptic sugar moieties as conserved targets for broad-spectrum virus neutralization and suggest the GNA-model of glycan-binding warrants focused investigation. View Full-Text
Keywords: carbohydrate microarrays; oligomannoses; AGOR; ASOR; GNA; 2G12; HIV-1; HCMV; SARS-CoV carbohydrate microarrays; oligomannoses; AGOR; ASOR; GNA; 2G12; HIV-1; HCMV; SARS-CoV
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Wang, D.; Tang, J.; Tang, J.; Wang, L.-X. Targeting N-Glycan Cryptic Sugar Moieties for Broad-Spectrum Virus Neutralization: Progress in Identifying Conserved Molecular Targets in Viruses of Distinct Phylogenetic Origins. Molecules 2015, 20, 4610-4622.

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