Dengue Virus Glycosylation: What Do We Know?

In many infectious diseases caused by either viruses or bacteria, pathogen glycoproteins play important roles during the infection cycle, ranging from entry to successful intracellular replication and host immune evasion. Dengue is no exception. Dengue virus glycoproteins, envelope protein (E) and non-structural protein 1 (NS1) are two popular sub-unit vaccine candidates. E protein on the virion surface is the major target of neutralizing antibodies. NS1 which is secreted during DENV infection has been shown to induce a variety of host responses through its binding to several host factors. However, despite their critical role in disease and protection, the glycosylated variants of these two proteins and their biological importance have remained understudied. In this review, we seek to provide a comprehensive summary of the current knowledge on protein glycosylation in DENV, and its role in virus biogenesis, host cell receptor interaction and disease pathogenesis.

• Publication year

  2017

• Venue

  Frontiers in Microbiology

• Publication date

  2017-07-25

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fmicb.2017.01415PMID 28791003PMCID 5524768
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• N-linked glycan in tick-borne encephalitis virus envelope protein affects viral secretion in mammalian cells, but not in tick cells. article (author version)

  2018cited by this paper
• Site-Specific N- and O-Glycopeptide Analysis Using an Integrated C18-PGC-LC-ESI-QTOF-MS/MS Approach.

  2017cited by this paper
• Complement in disease: a defence system turning offensive

  2016influential reference
• Maturing Glycoproteomics Technologies Provide Unique Structural Insights into the N-glycoproteome and Its Regulation in Health and Disease*

  2016cited by this paper
• Inhibition of endoplasmic reticulum glucosidases is required for in vitro and in vivo dengue antiviral activity by the iminosugar UV-4

  2016cited by this paper
• Hybrid mass spectrometry approaches in glycoprotein analysis and their usage in scoring biosimilarity

  2016cited by this paper
• Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy

  2016cited by this paper
• Dengue Virus Infection Is through a Cooperative Interaction between a Mannose Receptor and CLEC5A on Macrophage as a Multivalent Hetero-Complex

  2016cited by this paper
• Secreted NS1 Protects Dengue Virus from Mannose-Binding Lectin–Mediated Neutralization

  2016influential reference
• Challenges of glycosylation analysis and control: an integrated approach to producing optimal and consistent therapeutic drugs.

  2016cited by this paper
• Iminosugars Inhibit Dengue Virus Production via Inhibition of ER Alpha-Glucosidases—Not Glycolipid Processing Enzymes

  2016cited by this paper
• Characterization of N-Glycan Structures on the Surface of Mature Dengue 2 Virus Derived from Insect Cells

  2015influential reference
• Development of the Sanofi Pasteur tetravalent dengue vaccine: One more step forward.

  2015cited by this paper
• Site-specific characterization of envelope protein N-glycosylation on Sanofi Pasteur's tetravalent CYD dengue vaccine.

  2015influential reference
• Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity

  2015influential reference
• Efficacy of a tetravalent dengue vaccine in children in Latin America.

  2015cited by this paper
• Glycomic characterization of basal tears and changes with diabetes and diabetic retinopathy.

  2015cited by this paper
• Efficacy of a Tetravalent Dengue Vaccine in Children in Latin America.

  2015cited by this paper
• Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination

  2015influential reference
• Parasite Glycobiology: A Bittersweet Symphony

  2015cited by this paper
• The HIV glycan shield as a target for broadly neutralizing antibodies

  2015influential reference
• The Roles of Direct Recognition by Animal Lectins in Antiviral Immunity and Viral Pathogenesis

  2015cited by this paper
• Flavivirus NS1 Structures Reveal Surfaces for Associations with Membranes and the Immune System

  2014influential reference
• N- and O-glycosylation analysis of etanercept using liquid chromatography and quadrupole time-of-flight mass spectrometry equipped with electron-transfer dissociation functionality.

  2014cited by this paper
• Dengue Antibody-Dependent Enhancement: Knowns and Unknowns

  2014cited by this paper
• Revisiting dengue virus-host cell interaction: new insights into molecular and cellular virology.

  2014influential reference
• Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial.

  2014influential reference
• Two Distinct Sets of NS2A Molecules Are Responsible for Dengue Virus RNA Synthesis and Virion Assembly

  2014cited by this paper
• A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus

  2014cited by this paper
• The flavivirus NS1 protein: molecular and structural biology, immunology, role in pathogenesis and application as a diagnostic biomarker.

  2013influential reference
• Glycosylations in the Globular Head of the Hemagglutinin Protein Modulate the Virulence and Antigenic Properties of the H1N1 Influenza Viruses

  2013influential reference
• N-linked glycan in tick-borne encephalitis virus envelope protein affects viral secretion in mammalian cells, but not in tick cells.

  2013cited by this paper
• Thematic Minireview Series on Glycobiology and Extracellular Matrices: Glycan Functions Pervade Biology at All Levels*

  2013cited by this paper
• The Potent and Broadly Neutralizing Human Dengue Virus-Specific Monoclonal Antibody 1C19 Reveals a Unique Cross-Reactive Epitope on the bc Loop of Domain II of the Envelope Protein

  2013cited by this paper
• Structural analysis of glycoprotein sialylation – part II: LC-MS based detection

  2013cited by this paper
• Exploring site-specific N-glycosylation microheterogeneity of haptoglobin using glycopeptide CID tandem mass spectra and glycan database search.

  2013cited by this paper
• An iminosugar with potent inhibition of dengue virus infection in vivo.

  2013cited by this paper
• Glycomic Analysis of Human Respiratory Tract Tissues and Correlation with Influenza Virus Infection

  2013cited by this paper
• CLEC5A is critical for dengue virus-induced inflammasome activation in human macrophages.

  2013cited by this paper
• Determination of site-specific glycan heterogeneity on glycoproteins

  2012cited by this paper
• Structure of the dengue virus glycoprotein non-structural protein 1 by electron microscopy and single-particle analysis.

  2012cited by this paper
• Comparative structural analysis of the glycosylation of salivary and buccal cell proteins: innate protection against infection by Candida albicans.

  2012cited by this paper
• Crucial role of the N-glycans on the viral E-envelope glycoprotein in DC-SIGN-mediated dengue virus infection.

  2012influential reference
• Evidence for a Genetic and Physical Interaction between Nonstructural Proteins NS1 and NS4B That Modulates Replication of West Nile Virus

  2012cited by this paper
• The lectin pathway of complement activation contributes to protection from West Nile virus infection.

  2011cited by this paper
• Complement-Mediated Neutralization of Dengue Virus Requires Mannose-Binding Lectin

  2011cited by this paper
• Secreted dengue virus nonstructural protein NS1 is an atypical barrel-shaped high-density lipoprotein

  2011influential reference
• N-linked glycosylation of dengue virus NS1 protein modulates secretion, cell-surface expression, hexamer stability, and interactions with human complement.

  2011influential reference
• N-Glycans Modulate the Function of Human Corticosteroid-Binding Globulin*

  2011cited by this paper
• A Summary of

  2011influential reference
• Next generation dengue vaccines: a review of candidates in preclinical development.

  2011cited by this paper
• Similarities and Differences in the Glycosylation Mechanisms in Prokaryotes and Eukaryotes

  2011cited by this paper
• Utilizing ion-pairing hydrophilic interaction chromatography solid phase extraction for efficient glycopeptide enrichment in glycoproteomics.

  2010cited by this paper
• The dengue virus type 2 envelope protein fusion peptide is essential for membrane fusion.

  2010cited by this paper
• Simultaneous Glycan-Peptide Characterization Using Hydrophilic Interaction Chromatography and Parallel Fragmentation by CID, Higher Energy Collisional Dissociation, and Electron Transfer Dissociation MS Applied to the N-Linked Glycoproteome of Campylobacter jejuni*

  2010cited by this paper
• Lectins as pattern recognition molecules: the effects of epitope density in innate immunity.

  2010cited by this paper
• First cases of autochthonous dengue fever and chikungunya fever in France: from bad dream to reality!

  2010cited by this paper
• Dengue: a continuing global threat

  2010cited by this paper
• Both E Protein Glycans Adversely Affect Dengue Virus Infectivity but Are Beneficial for Virion Release

  2010influential reference
• Antagonism of the complement component C4 by flavivirus nonstructural protein NS1

  2010cited by this paper
• A systematic approach to protein glycosylation analysis: a path through the maze.

  2010cited by this paper
• Direct complement restriction of flavivirus infection requires glycan recognition by mannose-binding lectin.

  2010cited by this paper
• N-linked glycans on dengue viruses grown in mammalian and insect cells.

  2009influential reference
• Association of the pr Peptides with Dengue Virus at Acidic pH Blocks Membrane Fusion

  2009cited by this paper
• Essentials of glycobiology

  2009influential reference
• Increasing the sialylation of therapeutic glycoproteins: the potential of the sialic acid biosynthetic pathway.

  2009cited by this paper
• Characterization of Asn130-to-Ala mutant of dengue type 1 virus NS1 protein

  2008influential reference
• Role of Dendritic Cells in Antibody-Dependent Enhancement of Dengue Virus Infection

  2008cited by this paper
• CLEC5A is critical for dengue-virus-induced lethal disease

  2008influential reference
• Glycoproteomics and glycomics investigation of membrane N‐glycosylproteins from human colon carcinoma cells

  2008cited by this paper
• The Mannose Receptor Mediates Dengue Virus Infection of Macrophages

  2008influential reference
• The Glycosylation Capacity of Insect Cells

  2008influential reference
• Structure of the Immature Dengue Virus at Low pH Primes Proteolytic Maturation

  2008cited by this paper
• The Flavivirus Precursor Membrane-Envelope Protein Complex: Structure and Maturation

  2008cited by this paper
• Of cascades and perfect storms: the immunopathogenesis of dengue haemorrhagic fever‐dengue shock syndrome (DHF/DSS)

  2007influential reference
• The Non-structural Protein 4A of Dengue Virus Is an Integral Membrane Protein Inducing Membrane Alterations in a 2K-regulated Manner*

  2007cited by this paper
• Virus glycosylation: role in virulence and immune interactions

  2007cited by this paper
• Secreted NS1 of Dengue Virus Attaches to the Surface of Cells via Interactions with Heparan Sulfate and Chondroitin Sulfate E

  2007cited by this paper
• Essential Role of Dengue Virus Envelope Protein N Glycosylation at Asparagine-67 during Viral Propagation

  2007influential reference
• Protein N-glycosylation in the baculovirus-insect cell system.

  2007influential reference
• Glycosylation of the dengue 2 virus E protein at N67 is critical for virus growth in vitro but not for growth in intrathoracically inoculated Aedes aegypti mosquitoes.

  2007influential reference
• Avian flu: Influenza virus receptors in the human airway

  2006cited by this paper
• Modulation of Neural Carbohydrate Epitope Expression in Drosophila melanogaster Cells*

  2006cited by this paper
• Reconstitution in vitro of the GDP‐fucose biosynthetic pathways of Caenorhabditis elegans and Drosophila melanogaster

  2006cited by this paper
• The glycosylation site in the envelope protein of West Nile virus (Sarafend) plays an important role in replication and maturation processes.

  2006cited by this paper
• Cryo-EM reconstruction of dengue virus in complex with the carbohydrate recognition domain of DC-SIGN.

  2006cited by this paper
• Flavivirus entry into cultured mosquito cells and human peripheral blood monocytes

  2005cited by this paper
• The asialoglycoprotein receptor clears glycoconjugates terminating with sialic acidα2,6GalNAc

  2005cited by this paper
• The C‐type lectin‐like domain superfamily

  2005cited by this paper
• A comparative study of entry modes into C6/36 cells by Semliki Forest and Japanese encephalitis viruses

  2005cited by this paper
• Deglycosylation of the NS1 protein of dengue 2 virus, strain 16681: Construction and characterization of mutant viruses

  2005influential reference
• The role of the mannose-binding lectin in innate immunity.

  2005cited by this paper
• Variation in distribution of the three flavivirus-specified glycoproteins detected by immunofluorescence in infected Vero cells

  2005cited by this paper
• The asialoglycoprotein receptor clears glycoconjugates terminating with sialic acid alpha 2,6GalNAc.

  2005cited by this paper
• Structure of the dengue virus envelope protein after membrane fusion

  2004influential reference
• HCV E2 glycoprotein: mutagenesis of N-linked glycosylation sites and its effects on E2 expression and processing.

  2004cited by this paper
• Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells

  2004cited by this paper
• Conformational changes of the flavivirus E glycoprotein.

  2004cited by this paper
• Fragmentation of N-linked glycans with a matrix-assisted laser desorption/ionization ion trap time-of-flight mass spectrometer.

  2004cited by this paper
• Dendritic‐cell‐specific ICAM3‐grabbing non‐integrin is essential for the productive infection of human dendritic cells by mosquito‐cell‐derived dengue viruses

  2003influential reference

• Multiscale Simulations and Cryo-Electron Microscopy Reveal the Transition Pathway of Dengue Virus-like Particle Nanoassembly.

  2026cites this paper
• Glycosylated NS3/NS3A protein of bluetongue virus facilitates efficient viral egress via lipid raft anchoring

  2026cites this paper
• Exploring Small-Molecule Inhibitors of Glucosidase II: Advances, Challenges, and Therapeutic Potential in Cancer and Viral Infection

  2025cites this paper
• Chemometric Methods Applied to Infrared and Raman Spectroscopy for Arboviruses Diagnosis: A Systematic Review With Meta‐Analysis

  2025cites this paper
• Glycosylation in invertebrate immunity: Host response and pathogen evasion strategies.

  2025cites this paper
• GLYCO-BUILD: an enzymatic pipeline for the synthesis of peptides carrying eukaryotic N-glycans

  2025influential citation
• The novel design of a multi-epitope vaccine candidate against the dengue virus using advanced immunoinformatics and structural analysis

  2025cites this paper
• In-silico identification of host-key-genes associated with dengue-virus-infections highlighting their pathogenetic mechanisms and therapeutic agents

  2025cites this paper
• Fc-Mediated Effector Functions of Anti-NS1 Antibodies in Dengue

  2025cites this paper
• Factors determining the outcomes of immune imprinting after repeated orthoflavivirus infections

  2025cites this paper
• Unravelling dengue: insights from epidemiology, virology, diagnostics, vaccines and control

  2025cites this paper
• Overcoming dengue vaccine challenges through next-generation virus-like particle immunization strategies

  2025cites this paper
• Pathogenicity and virulence of Powassan virus

  2025cites this paper
• The hidden impact of producer cells on virion composition and infectivity.

  2025cites this paper
• Evolution and adaptation of dengue virus in response to high-temperature passaging in mosquito cells

  2025cites this paper
• ANCORAGEM MOLECULAR COM BASE NO ABACAVIR: ESTRATÉGIA DE MODIFICAÇÃO ESTRUTURAL DE PRÓ FÁRMACO PARA COMBATER A DENGUE

  2025cites this paper
• Alpha‐mannosidase‐2 modulates arbovirus infection in a pathogen‐ and Wolbachia‐specific manner in Aedes aegypti mosquitoes

  2024cites this paper
• Biothermodynamic analysis of the Dengue virus: Empirical formulas, biosynthesis reactions and thermodynamic properties of antigen-receptor binding and biosynthesis

  2024cites this paper
• A curious case of a negative control line on a dengue duo assay due to interference – A case report

  2024cites this paper
• The glycosylation deficiency of flavivirus NS1 attenuates virus replication through interfering with the formation of viral replication compartments

  2024cites this paper
• Dengue virus pathogenesis and host molecular machineries

  2024cites this paper
• Culicoides-Specific Fitness Increase of Vesicular Stomatitis Virus in Insect-to-Insect Infections

  2024cites this paper
• The cytoplasmic N-terminal tail of Zika virus NS4A protein forms oligomers in the absence of detergent or lipids

  2023cites this paper
• Antibody and Cell-Based Therapies against Virus-Induced Cancers in the Context of HIV/AIDS

  2023cites this paper
• Roles of NS1 Protein in Flavivirus Pathogenesis.

  2023cites this paper
• N-linked glycosylation of flavivirus E protein contributes to viral particle formation

  2023cites this paper
• An in-silico receptor-pharmacophore based multistep molecular docking and simulation study to evaluate the inhibitory potentials against NS1 of DENV-2

  2023cites this paper
• Antibody-Dependent Enhancement with a Focus on SARS-CoV-2 and Anti-Glycan Antibodies

  2023cites this paper
• Liang-Ge-San inhibits dengue virus serotype 2 infection by reducing caveolin1-induced cytoplasmic heat shock protein 70 translocation into the plasma membrane.

  2023cites this paper
• NS1 Protein N-Linked Glycosylation Site Affects the Virulence and Pathogenesis of Dengue Virus

  2023cites this paper
• Establishment of a CPER reverse genetics system for Powassan virus defines attenuating NS1 glycosylation sites and an infectious NS1-GFP11 reporter virus

  2023cites this paper
• Assessing Aedes aegypti candidate genes during viral infection and Wolbachia‐mediated pathogen blocking

  2022cites this paper
• New insights into the recombinant proteins and monoclonal antibodies employed to immunodiagnosis and control of Zika virus infection: A review.

  2022cites this paper
• Murine models of dengue virus infection for novel drug discovery

  2022cites this paper
• The role of protein glycosylation in muscle diseases

  2022cites this paper
• Glycosylation of viral proteins: Implication in virus–host interaction and virulence

  2022influential citation
• Identification of neo-andrographolide compound targeting NS1 Lys14: an important residue in NS1 activity driving dengue pathogenesis

  2022cites this paper
• Generation of soluble, cleaved, well-ordered, native-like dimers of dengue virus 4 envelope protein ectodomain (sE) suitable for vaccine immunogen design.

  2022cites this paper
• Exploring the Potential of Chemical Inhibitors for Targeting Post-translational Glycosylation of Coronavirus (SARS-CoV-2)

  2022cites this paper
• The ganglioside GM1a functions as a coreceptor/attachment factor for dengue virus during infection

  2022cites this paper
• Immuno-dominant dengue NS1 peptides as antigens for production of monoclonal antibodies

  2022cites this paper
• Computational approaches for innovative anti-viral drug discovery using Orthosiphon aristatus blume miq against dengue virus

  2022cites this paper
• Les polymères de mannose en production animale. 1. focus sur les structures chimiques rencontrées dans les aliments et les propriétés biologiques

  2021cites this paper
• Trimerization of the N-Terminal Tail of Zika Virus NS4A Protein: A Potential In Vitro Antiviral Screening Assay

  2021cites this paper
• Flavivirus infections induce a Golgi stress response in vertebrate and mosquito cells

  2021cites this paper
• Site-specific N-glycosylation analysis of animal cell culture-derived Zika virus proteins

  2021cites this paper
• Glycosylation on envelope glycoprotein of duck Tembusu virus affects virus replication in vitro and contributes to the neurovirulence and pathogenicity in vivo

  2021cites this paper
• Dengue fusion peptide in Langmuir monolayers: A binding parameter study.

  2021cites this paper
• Structural and Biochemical Insights Into Flavivirus Proteins.

  2021cites this paper
• Genotype-specific Features Reduce the Susceptibility of South American Yellow Fever Virus Strains to Vaccine-Induced Antibodies

  2021cites this paper
• Tropical Diseases of the Skin

  2021cites this paper
• Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: An update for 2017-2018.

  2021cites this paper
• Unconventional secretion of unglycosylated ORF8 is critical for the cytokine storm during SARS-CoV-2 infection

  2021cites this paper
• Relative contribution of nonstructural protein 1 in dengue pathogenesis

  2020cites this paper
• The Structure of the Membrane Protein of SARS-CoV-2 Resembles the Sugar Transporter SemiSWEET

  2020cites this paper
• SERINC5 Inhibits the Secretion of Complete and Genome-Free Hepatitis B Virions Through Interfering With the Glycosylation of the HBV Envelope

  2020cites this paper
• Principles of dengue virus evolvability derived from genotype-fitness maps in human and mosquito cells

  2020cites this paper
• Flavivirus Envelope Protein Glycosylation: Impacts on Viral Infection and Pathogenesis

  2020cites this paper
• A Genome-Wide CRISPR-Cas9 Screen Identifies the Dolichol-Phosphate Mannose Synthase Complex as a Host Dependency Factor for Dengue Virus Infection

  2020cites this paper
• Latest Updates in Dengue Fever Therapeutics: Natural, Marine, and Synthetic Drugs.

  2020cites this paper
• Enhancement of Infectivity of Insect Cell-Derived La Crosse Virus by Human Serum.

  2020cites this paper
• Synthetic Carbohydrate Chemistry and Translational Medicine.

  2020cites this paper
• Optimization of Recombinant Flavivirus Antigens for Infection Serology: Towards Syndrome-Based Multiplex Tests

  2020cites this paper
• Releasing Intracellular NS1 from Mosquito Cells for the Detection of Dengue Virus-Infected Mosquitoes

  2020cites this paper
• Structure-guided paradigm shifts in flavivirus assembly and maturation mechanisms

  2020cites this paper
• An update on dengue vaccine development, challenges, and future perspectives

  2020cites this paper
• Iminosugars: A host-targeted approach to combat Flaviviridae infections

  2020cites this paper
• Screening siRNAs against host glycosylation pathways to develop novel antiviral agents against hepatitis B virus

  2020cites this paper
• 1 Hijacking the Host Immune Cells by Dengue Virus : 2 Molecular Interplay of Receptors and Dengue Virus 3 Envelope 4 1

  2019influential citation
• Quantifying the RNA cap epitranscriptome reveals novel caps in cellular and viral RNA

  2019cites this paper
• Recent update on anti-dengue drug discovery.

  2019cites this paper
• Glycosylation of Zika Virus Is Important in Host-Virus Interaction and Pathogenesis

  2019cites this paper
• Accelerated Synthesis of Surface Functionalized Mannosylated Dendrimers Built on Cyclotriphosphazene Core

  2019cites this paper
• Molecular characteristics and replication mechanism of dengue, zika and chikungunya arboviruses, and their treatments with natural extracts from plants: An updated review

  2019cites this paper
• Glycosylation of Zika Virus is Important in Host–Virus Interaction and Pathogenic Potential

  2019cites this paper
• Human protein paucimannosylation: cues from the eukaryotic kingdoms

  2019cites this paper
• An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) and Non-Structural Protein 1 (NS1) Confers Complete Protection against Lethal Challenge in a Mouse Model

  2019cites this paper
• Hijacking the Host Immune Cells by Dengue Virus: Molecular Interplay of Receptors and Dengue Virus Envelope

  2019cites this paper
• Secretion of Nonstructural Protein 1 of Dengue Virus from Infected Mosquito Cells: Facts and Speculations

  2018cites this paper
• Caractérisation de la protéine S du coronavirus humain 229E

  2018cites this paper
• Discovery of Dengue Virus Inhibitors.

  2018cites this paper
• Transgenic mosquitoes for controlling transmission of arboviruses

  2017cites this paper
• Culicoides -Speci fi c Fitness Increase of Vesicular Stomatitis Virus in Insect-to-Insect Infections

  year unknowncites this paper