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A strategy for O-glycoproteomics of enveloped viruses--the O-glycoproteome of herpes simplex virus type 1.

ABSTRACT: Glycosylation of viral envelope proteins is important for infectivity and interaction with host immunity, however, our current knowledge of the functions of glycosylation is largely limited to N-glycosylation because it is difficult to predict and identify site-specific O-glycosylation. Here, we present a novel proteome-wide discovery strategy for O-glycosylation sites on viral envelope proteins using herpes simplex virus type 1 (HSV-1) as a model. We identified 74 O-linked glycosylation sites on 8 out of the 12 HSV-1 envelope proteins. Two of the identified glycosites found in glycoprotein B were previously implicated in virus attachment to immune cells. We show that HSV-1 infection distorts the secretory pathway and that infected cells accumulate glycoproteins with truncated O-glycans, nonetheless retaining the ability to elongate most of the surface glycans. With the use of precise gene editing, we further demonstrate that elongated O-glycans are essential for HSV-1 in human HaCaT keratinocytes, where HSV-1 produced markedly lower viral titers in HaCaT with abrogated O-glycans compared to the isogenic counterpart with normal O-glycans. The roles of O-linked glycosylation for viral entry, formation, secretion, and immune recognition are poorly understood, and the O-glycoproteomics strategy presented here now opens for unbiased discovery on all enveloped viruses.

SUBMITTER: Bagdonaite I

PROVIDER: S-EPMC4382219 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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A strategy for O-glycoproteomics of enveloped viruses--the O-glycoproteome of herpes simplex virus type 1.

Bagdonaite Ieva I Nordén Rickard R Joshi Hiren J HJ Dabelsteen Sally S Nyström Kristina K Vakhrushev Sergey Y SY Olofsson Sigvard S Wandall Hans H HH

PLoS pathogens 20150401 4

Glycosylation of viral envelope proteins is important for infectivity and interaction with host immunity, however, our current knowledge of the functions of glycosylation is largely limited to N-glycosylation because it is difficult to predict and identify site-specific O-glycosylation. Here, we present a novel proteome-wide discovery strategy for O-glycosylation sites on viral envelope proteins using herpes simplex virus type 1 (HSV-1) as a model. We identified 74 O-linked glycosylation sites o ...[more]

PMID: 25830354

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Dataset Information

A strategy for O-glycoproteomics of enveloped viruses--the O-glycoproteome of herpes simplex virus type 1.

Publications

A strategy for O-glycoproteomics of enveloped viruses--the O-glycoproteome of herpes simplex virus type 1.

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