Role of DC-SIGN in Lassa Virus Entry into Human Dendritic Cells

Goncalves, Ana-Rita; Moraz, Marie-Laurence; Pasquato, Antonella; Helenius, Ari; Lozach, Pierre-Yves et Kunz, Stefan (2013). Role of DC-SIGN in Lassa Virus Entry into Human Dendritic Cells Journal of Virology , vol. 87 , nº 21. pp. 11504-11515. DOI: 10.1128/jvi.01893-13.

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Résumé

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.

Type de document:	Article
Mots-clés libres:	lymphocytic choriomeningitis virus new-world arenaviruses c-type lectins alpha-dystroglycan old-world receptor recognition cellular receptor fever virus ebola-virus host-cell
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	08 mars 2016 21:22
Dernière modification:	08 mars 2016 21:22
URI:	https://espace.inrs.ca/id/eprint/2910

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