부산대학교 도서관

Crimean-Congo Hemorrhagic Fever Virus (CCHFV) and Hazara virus (HAZV) belong to the same viral serotype and family. HAZV has lately been used as a model system and surrogate to CCHFV. However, virus-host cell interaction and level of pathogenicity for these viruses are not well investigated nor compared. In this study, we compared HAZV and CCHFV infection of human polarized epithelial cells to shed light on similarities and differences in virus-host cell interaction between these two viruses. We investigated the pattern of infection of CCHFV and HAZV in fully polarized human cells, the Caco-2 cell line. Polarization of Caco-2 cells lead to difference in expression level and pattern of proteins between the apical and the basolateral membranes. We found that CCHFV virus, in contrast to HAZV, is more likely infecting polarized cells basolaterally. In addition, we found that cytokines/pro-inflammatory factors or other viral factors secreted from CCHFV infected moDC cells enhance the entry of CCHFV contrary to HAZV. We have shown that CCHFV and HAZV early in infection use different strategies for entry. The data presented in this study also highlight the important role of cytokines in CCHFV-host cell interaction. Author summary: Crimean-Congo Hemorrhagic Fever virus (CCHFV) is a tick-borne pathogen responsible for a severe acute fever disease in humans, requiring biosafety level 4 laboratory for handling. This is the reason why the molecular pathogenesis of CCHFV remains largely unknown. Hazara virus (HAZV), member of the same serogroup but nor responsible for human disease, is commonly used as surrogate model to study CCHFV in biosafety level 2 laboratory. As an important viral model, it is important to better understand its range of applicability. Using polarized Caco-2 cells, we showed HAZV doesn't have the same pattern of infection in fully polarized cells than CCHFV. These data were confirmed using compounds able to modulate cell junctions: compounds leaded to opposite effect on respective virus infection capacity. All data together suggest that CCHFV and HAZV receptors have different localization on polarized Caco-2 cells. Moreover, using supernatant of HAZV or CCHFV infected monocyte-derived dendritic cells, we demonstrated that only factors released from CCHFV-infected moDCs are able to enhance CCHFV infection. To our knowledge, this study is the first one showing differences in HAZV and CCHFV entry into polarized target cells and in CCHFV infection modulation by a paracrine effect linked to infected dendritic cells. [ABSTRACT FROM AUTHOR]