DC-SIGN as a receptor for phleboviruses

Pierre-Yves Lozach, Andreas Kühbacher, Roger Meier, Roberta Mancini, David Bitto, Michèle Bouloy, Ari Helenius

Research output: Contribution to journalArticle (Academic Journal)peer-review


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.

Original languageEnglish
Pages (from-to)75-88
Number of pages14
JournalCell Host & Microbe
Issue number1
Publication statusPublished - 21 Jul 2011


  • Bunyaviridae Infections/metabolism
  • Cell Adhesion Molecules/genetics
  • Dendritic Cells/metabolism
  • Endocytosis/physiology
  • Endosomes/metabolism
  • HeLa Cells/virology
  • Host-Pathogen Interactions
  • Humans
  • Lectins, C-Type/genetics
  • Mutation
  • Phlebovirus/metabolism
  • Polysaccharides/chemistry
  • Receptors, Cell Surface/genetics
  • Receptors, Virus/metabolism
  • Uukuniemi virus/metabolism
  • Virus Internalization


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