Usutu virus escapes langerin-induced restriction to productively infect human Langerhans cells, unlike West Nile virus - SFR Biosit - Biologie et Santé CNRS UMS 3480 Accéder directement au contenu
Article Dans Une Revue Emerging Microbes and Infections Année : 2022

Usutu virus escapes langerin-induced restriction to productively infect human Langerhans cells, unlike West Nile virus

Marine Seffals
Cécile Beck

Résumé

Usutu virus (USUV) and West Nile virus (WNV) are phylogenetically close emerging arboviruses transmitted by mosquitoes, and constitute a global public health threat. Since USUV and WNV enter the body through the skin, the first immune cells they encounter are skin-resident dendritic cells, the most peripheral outpost of immune defense. This unique network is composed of Langerhans cells (LCs) and dermal DCs, which reside in the epidermis and the dermis, respectively.Using human skin explants, we show that while both viruses can replicate in keratinocytes, they can also infect resident DCs with distinct tropism, since WNV preferentially infects DCs in the dermis, whereas USUV has a greater propensity to infect LCs. Using both purified human epidermal LCs (eLCs) and monocyte derived LCs (MoLCs), we confirm that LCs sustain a faster and more efficient replication of USUV compared with WNV and that this correlates with a more intense innate immune response to USUV compared with WNV. Next, we show that ectopic expression of the LC-specific C-type lectin receptor (CLR), langerin, in HEK293T cells allows WNV and USUV to bind and enter, but supports the subsequent replication of USUV only. Conversely, blocking or silencing langerin in MoLCs or eLCs made them resistant to USUV infection, thus demonstrating that USUV uses langerin to enter and replicate in LCs. Altogether, our results demonstrate that LCs constitute privileged target cells for USUV in human skin, because langerin favors its entry and replication. Intriguingly, this suggests that USUV efficiently escapes the antiviral functions of langerin, which normally safeguards LCs from most viral infections.
Fichier principal
Vignette du fichier
22221751.2022.pdf (3.95 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03595069 , version 1 (07-06-2022)

Licence

Paternité - Pas d'utilisation commerciale

Identifiants

Citer

Marie-France Martin, Ghizlane Maarifi, Hervé Abiven, Marine Seffals, Nicolas Mouchet, et al.. Usutu virus escapes langerin-induced restriction to productively infect human Langerhans cells, unlike West Nile virus. Emerging Microbes and Infections, 2022, 11 (1), pp.761-774. ⟨10.1080/22221751.2022.2045875⟩. ⟨hal-03595069⟩
102 Consultations
44 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More