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

Emerging Microbes and Infections

卷:0

Nathalie J. Arhel¹  Marie-France Martin¹  Ghizlane Maarifi¹  Hervé Abiven¹  Fabien P. Blanchet¹  Sébastien Nisole¹  Cécile Beck²  Yannick Simonin³  Nicolas Lévèque⁴  Charles Bodet⁴  Marine Seffals⁵  Nicolas Mouchet⁵ 

[1] Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier;

[2] Université Paris-Est;

[3] Université de Montpellier;

[4] Université de Poitiers;

[5] Université de Rennes 1;

关键词: west nile virus;    usutu virus;    langerhans cells;    langerin;    viral receptor;   

DOI  :  10.1080/22221751.2022.2045875

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown