An in vitro assay to study the molecular pathogenesis of Crimean-Congo hemorrhagic fever virus

Crimean-Congo hemorrhagic fever virus (CCHFV) causes severe acute human disease and its pathogenesis remains largely unknown. Some in vitro and in vivo models have been developed, but the relevance of the results remains limited by the models themself (animal cells and immunoincompetent mice). In this study, we established an in vitro model based on human polarized cell line in order to better characterize the mechanisms behind the molecular pathogenesis of CCHFV. Experiments were performed with CCHFV and the non-pathogenic Hazara virus (HAZV), closely related to CCHFV. We found that HAZV and CCHFV, although closely related, are different in their preference on site of entry, suggesting that CCHFV cell receptor(s) is(are) different to HAZV one(s) and may partially explain the difference of pathogenesis between the two viruses. Interestingly, we demonstrated the importance of including immune cells in in vitro models in order to get a more accurate picture of CCHFV pathogenesis using CCHFV-infected monocyte-derived dendritic cells (moDCs) or only their supernatant, we observed a changing in the preferred side of infection of CCHFV. This changing of entry pathway could be due to released soluble factors from the moDCs, resulting to a relocation of the receptor of CCHFV.