Role of DC-SIGN in Lassa virus entry into human dendritic cells. - RIIP - Réseau International des Instituts Pasteur Access content directly
Journal Articles Journal of Virology Year : 2013

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.

Dates and versions

pasteur-01131042 , version 1 (12-03-2015)

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Cite

Ana-Rita Goncalves, Marie-Laurence Moraz, Antonella Pasquato, Ari Helenius, Pierre-Yves Lozach, et al.. Role of DC-SIGN in Lassa virus entry into human dendritic cells.. Journal of Virology, 2013, 87 (21), pp.11504-15. ⟨10.1128/JVI.01893-13⟩. ⟨pasteur-01131042⟩

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