West Nile virus discriminates between DC-SIGN and DC-SIGNR for cellular attachment and infection

J Virol. 2006 Feb;80(3):1290-301. doi: 10.1128/JVI.80.3.1290-1301.2006.


The C-type lectins DC-SIGN and DC-SIGNR bind mannose-rich glycans with high affinity. In vitro, cells expressing these attachment factors efficiently capture, and are infected by, a diverse array of appropriately glycosylated pathogens, including dengue virus. In this study, we investigated whether these lectins could enhance cellular infection by West Nile virus (WNV), a mosquito-borne flavivirus related to dengue virus. We discovered that DC-SIGNR promoted WNV infection much more efficiently than did DC-SIGN, particularly when the virus was grown in human cell types. The presence of a single N-linked glycosylation site on either the prM or E glycoprotein of WNV was sufficient to allow DC-SIGNR-mediated infection, demonstrating that uncleaved prM protein present on a flavivirus virion can influence viral tropism under certain circumstances. Preferential utilization of DC-SIGNR was a specific property conferred by the WNV envelope glycoproteins. Chimeras between DC-SIGN and DC-SIGNR demonstrated that the ability of DC-SIGNR to promote WNV infection maps to its carbohydrate recognition domain. WNV virions and subviral particles bound to DC-SIGNR with much greater affinity than DC-SIGN. We believe this is the first report of a pathogen interacting more efficiently with DC-SIGNR than with DC-SIGN. Our results should lead to the discovery of new mechanisms by which these well-studied lectins discriminate among ligands.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding Sites
  • Cell Adhesion
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / physiology*
  • Cell Line
  • Cricetinae
  • Glycosylation
  • HeLa Cells
  • Humans
  • Lectins, C-Type / genetics
  • Lectins, C-Type / physiology*
  • Ligands
  • Mutation
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / physiology
  • Virulence
  • West Nile virus / genetics
  • West Nile virus / pathogenicity*
  • West Nile virus / physiology*


  • CLEC4M protein, human
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Ligands
  • Receptors, Cell Surface
  • Recombinant Proteins
  • Viral Envelope Proteins
  • prM protein, Flavivirus