title: Crucial role of the N-glycans on the viral E-envelope glycoprotein in DC-SIGN-mediated dengue virus infection.
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.
authors.affiliation: Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Marijke.Alen@rega.kuleuven.be
authors.forename: Marijke M F
authors.initials: MM
authors.lastname: Alen
authors.forename: Kai
authors.initials: K
authors.lastname: Dallmeier
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.forename: Dominique
authors.initials: D
authors.lastname: Schols
mesh_terms: D000330:Aedes / Q000166:cytology; D000373:Agglutinins / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology; D003715:Dengue / Q000378:metabolism / Q000821:virology*; D003716:Dengue Virus / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D024882:Drug Resistance, Viral; D005838:Genotype; D006031:Glycosylation; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism / Q000821:virology; D019668:Liliaceae / Q000737:chemistry; D009154:Mutation; D011134:Polysaccharides / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D020539:Sequence Analysis, Protein; D014162:Transfection; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000373:Agglutinins; D000998:Antiviral Agents; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D014759:Viral Envelope Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C051821:E-glycoprotein, Dengue virus type 2