Crucial role of the N-glycans on the viral E-envelope glycoprotein in DC-SIGN-mediated dengue virus infection

Marijke M F Alen; Kai Dallmeier; Jan Balzarini; Johan Neyts; Dominique Schols

doi:10.1016/j.antiviral.2012.10.007

Crucial role of the N-glycans on the viral E-envelope glycoprotein in DC-SIGN-mediated dengue virus infection

Antiviral Res. 2012 Dec;96(3):280-7. doi: 10.1016/j.antiviral.2012.10.007. Epub 2012 Oct 31.

Authors

Marijke M F Alen¹, Kai Dallmeier, Jan Balzarini, Johan Neyts, Dominique Schols

Affiliation

¹ Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Marijke.Alen@rega.kuleuven.be

PMID: 23124109
DOI: 10.1016/j.antiviral.2012.10.007

Abstract

We generated in the mosquito cell line C6/36 a dengue virus (DENV) resistant to Hippeastrum hybrid agglutinin (HHA), a carbohydrate-binding agent (CBA). The genotype and phenotype were characterized of the HHA resistant (HHA(res)) DENV compared to the wild-type (WT) DENV. Sequencing the structural proteins of HHA(res) resulted in two mutations, N67D and T155I, indicating a deletion of both N-glycosylation sites on the viral envelope E-glycoprotein. The HHA(res) DENV could replicate in mammalian and mosquito cells that are lacking dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) expression. In contrast, DC-SIGN expressing human cells namely monocyte-derived dendritic cells as well as DC-SIGN-transfected cells were no longer susceptible to HHA(res) DENV. This demonstrates a crucial role of the N-glycans in the E-glycoprotein in the infection of dendritic cells, which constitute primary target cells of DENV during viral pathogenesis in the human body.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aedes / cytology
Agglutinins / pharmacology
Animals
Antiviral Agents / pharmacology
Binding Sites
Cell Adhesion Molecules / metabolism*
Cell Differentiation
Chlorocebus aethiops
Dendritic Cells / metabolism
Dendritic Cells / virology
Dengue / metabolism
Dengue / virology*
Dengue Virus / drug effects
Dengue Virus / genetics
Dengue Virus / pathogenicity*
Drug Resistance, Viral
Genotype
Glycosylation
Humans
Lectins, C-Type / metabolism*
Leukocytes, Mononuclear / cytology
Leukocytes, Mononuclear / metabolism
Leukocytes, Mononuclear / virology
Liliaceae / chemistry
Mutation
Polysaccharides / metabolism*
Receptors, Cell Surface / metabolism*
Sequence Analysis, Protein
Transfection
Vero Cells
Viral Envelope Proteins / genetics
Viral Envelope Proteins / metabolism*
Virus Replication

Substances

Agglutinins
Antiviral Agents
Cell Adhesion Molecules
DC-specific ICAM-3 grabbing nonintegrin
E-glycoprotein, Dengue virus type 2
Lectins, C-Type
Polysaccharides
Receptors, Cell Surface
Viral Envelope Proteins