CONICET | Buscador de Institutos y Recursos Humanos

Hantaviruses are responsible for both Hemorrhagic Fever with Renal Syndrome (HFRS) and Hantavirus Pulmonary Syndrome (HPS). The main known target of infection are microvascular endothelial cells. Hantaan (HTNV) and Andes (ANDV) virus are representative strains responsible for HFRS and HPS, respectively. In previous studies, we observed a massive polyclonal activation of circulating B cells in HPS patients from Argentina. Thus, the aim of this study was to evaluate if and how hantavirus infected endothelial cells (EC) can have a role in B cell activation.To test this hypothesis B cells were co-cultured with HTNV-infected EC (HMVEC-L) both directly and with a transwell system. Additionally, B cells were exposed to conditioned medium from infected EC (HTNV-CM). As controls, EC were exposed to UV inactivated HTNV and medium alone. B cells were collected 24-72h post co-culture (p.c.c.) and assessed by flow cytometry.All HTNV-infected co-culture conditions showed elevated levels of CD69+ B cells compared to controls 24h p.c.c., and increased with time, suggesting that HTNV-EC secrete soluble activating factors. In line with this, augmented levels of CD71+ and BAFF-R+ B cells were also observed at 24h p.c.c. Interestingly, while BAFFR+ B cell levels decreased with time p.c.c. in controls, they remained elevated in the HTNV-CM condition. Together with this, higher levels of live B cells were observed at 72h in HTNV-CM vs controls, suggesting secretion of proliferative and/or survival factors for B cells by HTNV-EC. Furthermore, increased levels of IL-6 and BAFF -B cell activating and pro-survival cytokines- were detected in supernatants from HTNV-EC, constituting possible mediators of B cell activation by HTNV-EC.In conclusion, we show that hantavirus infected EC can activate B cells. These results reveal as well possible mechanisms that could be involved in the polyclonal activation of B cells observed in HPS patients.