Abstract
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.
Highlights
Crimean-Congo Hemorrhagic Fever virus (CCHFV) is a tick-borne pathogen responsible for a severe acute fever disease in humans with a fatality rate of 5–30%
Using polarized Caco-2 cells, we showed Hazara virus (HAZV) doesn’t have the same pattern of infection in fully polarized cells than CCHFV
We have shown that CCHFV are more likely to entrer and release on the basolateral side of highly polarized Madin-Darby Canine Kidney cell line (MDCK-1)[19]
Summary
Crimean-Congo Hemorrhagic Fever virus (CCHFV) is a tick-borne pathogen responsible for a severe acute fever disease in humans with a fatality rate of 5–30%. Apart from tick-bites, human to human transmission occurs through handling of infected animal blood or tissue. Several studies have shown that patients with the severe form of disease exhibit a high level of pro-inflammatory cytokines Some in vitro studies have confirmed the release of pro-inflammatory cytokines by CCHFV-infected human monocytesderived dendritic cells (moDCs) [12,13] and human endothelial cells [12,14]. The knowledge about the molecular pathogenesis of CCHFV is limited by biological and technical restrictions: i) handling CCHFV requires a biosafety level 4 laboratory (BSL-4), ii) no good in vitro or in vivo models are available, iii) most of CCHFV cases occur in remote regions where advanced medical structures are lacking
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