A Strategy for O-Glycoproteomics of Enveloped Viruses-the O-Glycoproteome of Herpes Simplex Virus Type 1

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.

Nordén, Rickard,1977Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine(Swepub:gu)xnorri (författare)
Joshi, H. J. (författare)
Dabelsteen, S. (författare)
Nyström, Kristina,1977Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine(Swepub:gu)xnystk (författare)
Vakhrushev, S. Y. (författare)
Olofsson, Sigvard,1948Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine(Swepub:gu)xolosi (författare)
Wandall, H. H. (författare)
Göteborgs universitetInstitutionen för biomedicin, avdelningen för infektionssjukdomar (creator_code:org_t)

Av författaren/redakt...: Bagdonaite, I.; Nordén, Rickard, ...; Joshi, H. J.; Dabelsteen, S.; Nyström, Kristin ...; Vakhrushev, S. Y ...; visa fler...; Olofsson, Sigvar ...; Wandall, H. H.; visa färre...

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