Role of DC-SIGN in Lassa virus entry into human dendritic cells

J Virol. 2013 Nov;87(21):11504-15. doi: 10.1128/JVI.01893-13. Epub 2013 Aug 21.

Abstract

The arenavirus Lassa virus (LASV) causes a severe hemorrhagic fever with high mortality in humans. Antigen-presenting cells, in particular dendritic cells (DCs), are early and preferred targets of LASV, and their productive infection contributes to the virus-induced immunosuppression observed in fatal disease. Here, we characterized the role of the C-type lectin DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) in LASV entry into primary human DCs using a chimera of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) expressing the LASV glycoprotein (rLCMV-LASVGP). We found that differentiation of human primary monocytes into DCs enhanced virus attachment and entry, concomitant with the upregulation of DC-SIGN. LASV and rLCMV-LASVGP bound to DC-SIGN via mannose sugars located on the N-terminal GP1 subunit of LASVGP. We provide evidence that DC-SIGN serves as an attachment factor for rLCMV-LASVGP in monocyte-derived immature dendritic cells (MDDC) and can accelerate the capture of free virus. However, in contrast to the phlebovirus Uukuniemi virus (UUKV), which uses DC-SIGN as an authentic entry receptor, productive infection with rLCMV-LASVGP was less dependent on DC-SIGN. In contrast to the DC-SIGN-mediated cell entry of UUKV, entry of rLCMV-LASVGP in MDDC was remarkably slow and depended on actin, indicating the use of different endocytotic pathways. In sum, our data reveal that DC-SIGN can facilitate cell entry of LASV in human MDDC but that its role seems distinct from the function as an authentic entry receptor reported for phleboviruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion Molecules / metabolism*
  • Cells, Cultured
  • Dendritic Cells / virology*
  • Host-Pathogen Interactions*
  • Humans
  • Lassa virus / genetics
  • Lassa virus / physiology*
  • Lectins, C-Type / metabolism*
  • Lymphocytic choriomeningitis virus / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, Virus / metabolism
  • Virus Internalization*

Substances

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