Details

Autor(en) / Beteiligte

• Bagdonaite, Ieva
• Nordén, Rickard
• Joshi, Hiren J
• Dabelsteen, Sally
• Nyström, Kristina
• Vakhrushev, Sergey Y
• Olofsson, Sigvard
• Wandall, Hans H
• Rey, Félix A.

Titel

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

Ist Teil von

• PLoS pathogens, 2015-04, Vol.11 (4), p.e1004784-e1004784

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.