Format

Send to

Choose Destination
J Biol Chem. 2016 Jun 3;291(23):12014-28. doi: 10.1074/jbc.M116.721746. Epub 2016 Apr 15.

Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus.

Author information

1
From the Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark and.
2
the Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, 413 45 Gothenburg, Sweden.
3
From the Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark and hhw@sund.ku.dk.

Abstract

Herpesviruses are among the most complex and widespread viruses, infection and propagation of which depend on envelope proteins. These proteins serve as mediators of cell entry as well as modulators of the immune response and are attractive vaccine targets. Although envelope proteins are known to carry glycans, little is known about the distribution, nature, and functions of these modifications. This is particularly true for O-glycans; thus we have recently developed a "bottom up" mass spectrometry-based technique for mapping O-glycosylation sites on herpes simplex virus type 1. We found wide distribution of O-glycans on herpes simplex virus type 1 glycoproteins and demonstrated that elongated O-glycans were essential for the propagation of the virus. Here, we applied our proteome-wide discovery platform for mapping O-glycosites on representative and clinically significant members of the herpesvirus family: varicella zoster virus, human cytomegalovirus, and Epstein-Barr virus. We identified a large number of O-glycosites distributed on most envelope proteins in all viruses and further demonstrated conserved patterns of O-glycans on distinct homologous proteins. Because glycosylation is highly dependent on the host cell, we tested varicella zoster virus-infected cell lysates and clinically isolated virus and found evidence of consistent O-glycosites. These results present a comprehensive view of herpesvirus O-glycosylation and point to the widespread occurrence of O-glycans in regions of envelope proteins important for virus entry, formation, and recognition by the host immune system. This knowledge enables dissection of specific functional roles of individual glycosites and, moreover, provides a framework for design of glycoprotein vaccines with representative glycosylation.

PMID:
27129252
PMCID:
PMC4933254
DOI:
10.1074/jbc.M116.721746
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center