title: DC-SIGN as a receptor for phleboviruses.
abstract: During natural transmission, bunyaviruses are introduced into the skin through arthropod bites, and dermal dendritic cells (DCs) are the first to encounter incoming viruses. DC-SIGN is a C-type lectin highly expressed on the surface of dermal DCs. We found that several arthropod-borne phleboviruses (Bunyaviridae), including Rift Valley fever and Uukuniemi viruses, exploit DC-SIGN to infect DCs and other DC-SIGN-expressing cells. DC-SIGN binds the virus directly via interactions with high-mannose N-glycans on the viral glycoproteins and is required for virus internalization and infection. In live cells, virus-induced clustering of cell surface DC-SIGN could be visualized. An endocytosis-defective mutant of DC-SIGN was unable to mediate virus uptake, indicating that DC-SIGN is an authentic receptor required for both attachment and endocytosis. After internalization, viruses separated from DC-SIGN and underwent trafficking to late endosomes. Our study provides real-time visualization of virus-receptor interactions on the cell surface and establishes DC-SIGN as a phlebovirus entry receptor.
authors.affiliation: Institute of Biochemistry, ETH Zurich, Schafmattstrasse 18, CH-8093 Zurich, Switzerland. lozach@bc.biol.ethz.ch
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Lozach
authors.forename: Andreas
authors.initials: A
authors.lastname: Kühbacher
authors.forename: Roger
authors.initials: R
authors.lastname: Meier
authors.forename: Roberta
authors.initials: R
authors.lastname: Mancini
authors.forename: David
authors.initials: D
authors.lastname: Bitto
authors.forename: Michèle
authors.initials: M
authors.lastname: Bouloy
authors.forename: Ari
authors.initials: A
authors.lastname: Helenius
mesh_terms: D002044:Bunyaviridae Infections / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology*; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism; D006367:HeLa Cells / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D016856:Phlebovirus / Q000378:metabolism* / Q000472:pathogenicity; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D018066:Uukuniemi virus / Q000378:metabolism / Q000472:pathogenicity; D053586:Virus Internalization; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin