The Crimean-Congo haemorrhagic fever virus hijacks the liver lipid metabolic pathway for virion production

The Crimean-Congo Haemorrhagic Fever Virus (CCHFV), a tri-segmented negative-strand virus that belongs to the <i>Orthonairovirus</i> genus, is highly pathogenic in humans but not in other host species. Following infection in humans, CCHFV disseminates widely but replicates most strongly in hepatocytes, indicating a preferential liver tropism. As hepatocytes are the primary site for production and secretion of lipids, here we sought to characterize the interplay between CCHFV and lipoprotein metabolism in hepatocytes. First, we found that CCHFV particles display a heterogeneous profile of density, suggesting various virion compositions. Next, we showed that several lipoprotein components are associated with viral particles. Additionally, we found that pharmacological inhibition or down-regulation of the host factors involved in lipoprotein biogenesis and lipid metabolism could impair CCHFV infection. Our results, therefore, by revealing a close interplay between liver lipid metabolism and CCHFV, highlight the potential of repurposing existing lipid-modulating drugs and allow designing new interventions to curb CCHFV infections.