title: DC-SIGN enhances infection of cells with glycosylated West Nile virus in vitro and virus replication in human dendritic cells induces production of IFN-alpha and TNF-alpha.
abstract: The recent introduction of West Nile virus (WNV) into the Western hemisphere resulted in significant human outbreaks causing disease of variable severity. Previous studies classified WNV into two major lineages (L1 and L2) that differ in their virulence. Since most L1 strains are glycosylated, we investigated the role of dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN) in infection efficiency of glycosylated WNV strains. We showed that glycosylated strains, in contrast to non-glycosylated strains, infected DC-SIGN expressing cells more efficiently than DC-SIGN negative cells. Furthermore, WNV can productively infect cultured human dendritic cells (DCs) and infection of dendritic cells with the glycosylated WNV-NY99 L1 strain induced production of significantly more TNF-alpha and IFN-alpha in cultured DC, than infection with the non-glycosylated B956 L2 strain. Together, these results indicate that DC-SIGN enhances infection of cells by WNV glycosylated strains, which may at least in part explain the higher pathogenicity of glycosylated L1 strains versus most non-glycosylated L2 strains.
authors.affiliation: Department of Virology, Erasmus Medical Center Rotterdam, Institute of Virology, PO Box 1738, 3000 DR Rotterdam, The Netherlands. b.martina@erasmusmc.nl
authors.forename: Byron E E
authors.initials: BE
authors.lastname: Martina
authors.forename: Penelopie
authors.initials: P
authors.lastname: Koraka
authors.forename: Petra
authors.initials: P
authors.lastname: van den Doel
authors.forename: Guus F
authors.initials: GF
authors.lastname: Rimmelzwaan
authors.forename: Bart L
authors.initials: BL
authors.lastname: Haagmans
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication; D014901:West Nile Fever / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014902:West Nile virus / Q000502:physiology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D016898:Interferon-alpha; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin