title: Role of DC-SIGN in Lassa virus entry into human dendritic cells.
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.
authors: Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
authors: Ana-Rita
authors: AR
authors: Goncalves
authors: Marie-Laurence
authors: ML
authors: Moraz
authors: Antonella
authors: A
authors: Pasquato
authors: Ari
authors: A
authors: Helenius
authors: Pierre-Yves
authors: PY
authors: Lozach
authors: Stefan
authors: S
authors: Kunz
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007836:Lassa virus / Q000235:genetics / Q000502:physiology*; D037181:Lectins, C-Type / Q000378:metabolism*; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D053586:Virus Internalization; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
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