Identification of Three Novel O-Linked Glycans in the Envelope Protein of Tick-Borne Encephalitis Virus

The tick-borne encephalitis virus is a pathogen endemic to northern Europe and Asia, transmitted through bites from infected ticks. It is a member of the <i>Flaviviridae</i> family and possesses a positive-sense, single-stranded RNA genome encoding a polypeptide that is processed into se...

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Main Authors: Ebba Könighofer, Ekaterina Mirgorodskaya, Kristina Nyström, Karin Stiasny, Ambjörn Kärmander, Tomas Bergström, Rickard Nordén
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/16/12/1891
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author Ebba Könighofer
Ekaterina Mirgorodskaya
Kristina Nyström
Karin Stiasny
Ambjörn Kärmander
Tomas Bergström
Rickard Nordén
author_facet Ebba Könighofer
Ekaterina Mirgorodskaya
Kristina Nyström
Karin Stiasny
Ambjörn Kärmander
Tomas Bergström
Rickard Nordén
author_sort Ebba Könighofer
collection DOAJ
description The tick-borne encephalitis virus is a pathogen endemic to northern Europe and Asia, transmitted through bites from infected ticks. It is a member of the <i>Flaviviridae</i> family and possesses a positive-sense, single-stranded RNA genome encoding a polypeptide that is processed into seven non-structural and three structural proteins, including the envelope (E) protein. The glycosylation of the E protein, involving a single N-linked glycan at position N154, plays a critical role in viral infectivity and pathogenesis. Here, we dissected the entire glycosylation profile of the E protein using liquid chromatography-tandem mass spectrometry and identified three novel O-linked glycans, which were found at relatively low frequency. One of the O-linked glycans was positioned close to the highly conserved N-linked glycan site, and structural analysis suggested that it may be relevant for the function of the E 150-loop. The N154 site was found to be glycosylated with a high frequency, containing oligomannose or complex-type structures, some of which were fucosylated. An unusually high portion of oligomannose N-linked glycan structures exhibited compositions that are normally observed on proteins when they are translocated from the endoplasmic reticulum to the trans-Golgi network, suggesting disruption of the glycan processing pathway in the infected cells from which the E protein was obtained.
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spelling doaj-art-7ae081ebf5f34187a55a200cbe85056f2025-08-20T02:01:15ZengMDPI AGViruses1999-49152024-12-011612189110.3390/v16121891Identification of Three Novel O-Linked Glycans in the Envelope Protein of Tick-Borne Encephalitis VirusEbba Könighofer0Ekaterina Mirgorodskaya1Kristina Nyström2Karin Stiasny3Ambjörn Kärmander4Tomas Bergström5Rickard Nordén6Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 413 46 Gothenburg, SwedenProteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, SwedenDepartment of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 413 46 Gothenburg, SwedenCenter for Virology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 413 46 Gothenburg, SwedenDepartment of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 413 46 Gothenburg, SwedenDepartment of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 413 46 Gothenburg, SwedenThe tick-borne encephalitis virus is a pathogen endemic to northern Europe and Asia, transmitted through bites from infected ticks. It is a member of the <i>Flaviviridae</i> family and possesses a positive-sense, single-stranded RNA genome encoding a polypeptide that is processed into seven non-structural and three structural proteins, including the envelope (E) protein. The glycosylation of the E protein, involving a single N-linked glycan at position N154, plays a critical role in viral infectivity and pathogenesis. Here, we dissected the entire glycosylation profile of the E protein using liquid chromatography-tandem mass spectrometry and identified three novel O-linked glycans, which were found at relatively low frequency. One of the O-linked glycans was positioned close to the highly conserved N-linked glycan site, and structural analysis suggested that it may be relevant for the function of the E 150-loop. The N154 site was found to be glycosylated with a high frequency, containing oligomannose or complex-type structures, some of which were fucosylated. An unusually high portion of oligomannose N-linked glycan structures exhibited compositions that are normally observed on proteins when they are translocated from the endoplasmic reticulum to the trans-Golgi network, suggesting disruption of the glycan processing pathway in the infected cells from which the E protein was obtained.https://www.mdpi.com/1999-4915/16/12/1891E proteinN-linked glycanO-linked glycantick-borne encephalitis virus
spellingShingle Ebba Könighofer
Ekaterina Mirgorodskaya
Kristina Nyström
Karin Stiasny
Ambjörn Kärmander
Tomas Bergström
Rickard Nordén
Identification of Three Novel O-Linked Glycans in the Envelope Protein of Tick-Borne Encephalitis Virus
Viruses
E protein
N-linked glycan
O-linked glycan
tick-borne encephalitis virus
title Identification of Three Novel O-Linked Glycans in the Envelope Protein of Tick-Borne Encephalitis Virus
title_full Identification of Three Novel O-Linked Glycans in the Envelope Protein of Tick-Borne Encephalitis Virus
title_fullStr Identification of Three Novel O-Linked Glycans in the Envelope Protein of Tick-Borne Encephalitis Virus
title_full_unstemmed Identification of Three Novel O-Linked Glycans in the Envelope Protein of Tick-Borne Encephalitis Virus
title_short Identification of Three Novel O-Linked Glycans in the Envelope Protein of Tick-Borne Encephalitis Virus
title_sort identification of three novel o linked glycans in the envelope protein of tick borne encephalitis virus
topic E protein
N-linked glycan
O-linked glycan
tick-borne encephalitis virus
url https://www.mdpi.com/1999-4915/16/12/1891
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