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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.
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https://hal-riip.archives-ouvertes.fr/pasteur-01131042
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Submitted on : Thursday, March 12, 2015 - 6:38:13 PM
Last modification on : Monday, May 25, 2020 - 8:54:02 PM

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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, American Society for Microbiology, 2013, 87 (21), pp.11504-15. ⟨10.1128/JVI.01893-13⟩. ⟨pasteur-01131042⟩

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