Characterization of the Viral O -Glycopeptidome: a Novel Tool of Relevance for Vaccine Design and Serodiagnosis
| Autor: | Ola Blixt, Sigvard Olofsson, Aaron S. Nudelman, Knud J. Jensen, Tomas Bergström, Emiliano Cló, Stjepan K. Kračun, Jan-Åke Liljeqvist |
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| Rok vydání: | 2012 |
| Předmět: |
Glycan
Glycosylation viruses Herpesvirus 2 Human Immunology Microbiology Epitope Epitopes chemistry.chemical_compound Immune system Viral Envelope Proteins Viral envelope Polysaccharides Immunity Virology Humans Serologic Tests Glycoproteins chemistry.chemical_classification Vaccines biology Computational Biology carbohydrates (lipids) chemistry Insect Science biology.protein Pathogenesis and Immunity Antibody Glycoprotein |
| Zdroj: | Journal of Virology. 86:6268-6278 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | Viral envelope proteins mediate interactions with host cells, leading to internalization and intracellular propagation. Envelope proteins are glycosylated and are known to serve important functions in masking host immunity to viral glycoproteins. However, the viral infectious cycle in cells may also lead to aberrant glycosylation that may elicit immunity. Our knowledge of immunity to aberrant viral glycans and glycoproteins is limited, potentially due to technical limitations in identifying immunogenic glycans and glycopeptide epitopes. This work describes three different complementary methods for high-throughput screening and identification of potential immunodominant O -glycopeptide epitopes on viral envelope glycoproteins: (i) on-chip enzymatic glycosylation of scan peptides, (ii) chemical glycopeptide microarray synthesis, and (iii) a one-bead-one-compound random glycopeptide library. We used herpes simplex virus type 2 (HSV-2) as a model system and identified a simple O -glycopeptide pan-epitope, 501 PPA(GalNAc)TAPG 507 , on the mature gG-2 glycoprotein that was broadly recognized by IgG antibodies in HSV-2-infected individuals but not in HSV-1-infected or noninfected individuals. Serum reactivity to the extended sialyl-T glycoform was tolerated, suggesting that self glycans can participate in immune responses. The methods presented provide new insight into viral immunity and new targets for immunodiagnostic and therapeutic measures. |
| Databáze: | OpenAIRE |
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