Metabolic reprogramming and host-immune response against Crimean-Congo Hemorrhagic Fever Viruses

Neogi, Ujjwal; Elaldi, Nazif; Appelberg, Sofia; Ambikan, Anoop T.; Kennedy, Emma; Dowall, Stuart; Bagci, Binnur K.; Gupta, Soham; Rodriguez, Jimmy E.; Svensson-Akusjärvi, Sara; Monteil, Vanessa M.; Végvári, Ákos; Weber, Friedemann; Hewson, Roger; Mirazimi, Ali

The pathogenesis and host-viral interactions of the Crimean–Congo hemorrhagic fever virus (CCHFV) are convoluted and have not been evaluated previously. To understand the host immune responses against CCHFV, we have performed a global transcriptomic analysis of peripheral blood mononuclear cells from a longitudinal cohort of CCHF patients who survived and temporal untargeted proteomics analysis of CCHFV infected cells. Our results indicate that during the acute phase of CCHFV infection, the host’s metabolic reprogramming towards central carbon metabolism including glycolysis/gluconeogenesis occurs. This could be regulated by the PI3K/Akt, HIF-1, FoxO, and AMPK signaling pathways and play a central role in viral replication. Moreover, key interferon stimulating genes (ISGs; ISG12, ISG15, ISG20 and MXs; Mx1 and Mx2) are activated during infection, suggesting a role for type I and II interferon-mediated antiviral mechanisms. Targeting type I interferon response through metabolic perturbation could be an attractive therapeutic intervention for CCHFV as well as aid as antiviral strategies.