title: The location of asparagine-linked glycans on West Nile virions controls their interactions with CD209 (dendritic cell-specific ICAM-3 grabbing nonintegrin).
abstract: Mammalian cell-derived West Nile virus preferentially infects cells expressing the C-type lectin CD209L (dendritic cellspecific ICAM-3 grabbing nonintegrin-related protein; liver- and lymph node-specific ICAM-3 grabbing nonintegrin) but not cells expressing CD209 (dendritic cell-specific ICAM-3 grabbing nonintegrin). In contrast, Dengue virus infection is enhanced in cells expressing either attachment factor. The West Nile virus envelope (E) protein contains a single N-linked glycosylation site at residue 154, whereas Dengue virus E contains sites at residues 153 and 67. We introduced a glycosylation site at position 67 into West Nile virus E. Reporter virus particles pseudotyped with this E protein infected cells using either CD209 or CD209L. We also introduced glycosylation sites at several novel positions. All sites allowed CD209L-mediated infection, but only a subset promoted CD209 use. As seen for other viruses, mannose-rich glycans on West Nile virus were required for its interactions with CD209. Surprisingly, however, mannose-rich glycans were not required for CD209L-mediated infection. Complex glycans, particularly N-acetylglucosamine-terminated structures, were able to mediate reporter virus particle interactions with CD209L. We propose that CD209L recognizes glycosylated flaviviruses with broad specificity, whereas CD209 is selective for flaviviruses bearing mannose-rich glycans. The location of the N-linked glycosylation sites on a virion determines the types of glycans incorporated, thus controlling viral tropism for CD209-expressing cells.
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Carl W
authors.initials: CW
authors.lastname: Davis
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mattei
authors.forename: Hai-Yen
authors.initials: HY
authors.lastname: Nguyen
authors.forename: Camilo
authors.initials: C
authors.lastname: Ansarah-Sobrinho
authors.forename: Robert W
authors.initials: RW
authors.lastname: Doms
authors.forename: Theodore C
authors.initials: TC
authors.lastname: Pierson
mesh_terms: D001216:Asparagine / Q000737:chemistry*; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D003716:Dengue Virus / Q000378:metabolism; D005416:Flavivirus / Q000378:metabolism; D017930:Genes, Reporter; D006031:Glycosylation; D006801:Humans; D016023:Integrins / Q000378:metabolism; D020014:K562 Cells; D037102:Lectins / Q000737:chemistry; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D008958:Models, Molecular; D011134:Polysaccharides / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D014902:West Nile virus / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D001216:Asparagine; D015815:Cell Adhesion Molecules; D016023:Integrins; D037102:Lectins; D037181:Lectins, C-Type; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin