DC-SIGN as a receptor for phleboviruses

Cell Host Microbe. 2011 Jul 21;10(1):75-88. doi: 10.1016/j.chom.2011.06.007.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Polysaccharides
  • Receptors, Cell Surface
  • Receptors, Virus