Multi-omics insights into host-viral response and pathogenesis in Crimean-Congo Hemorrhagic Fever Viruses for novel therapeutic target

Abstract

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.

Unraveling the Pathogenesis of Crimean-Congo Hemorrhagic Fever: A Novel Approach via Non-Targeted Metabolomics by NMR Spectroscopy

“…Metabolomics has emerged as a pivotal approach for inspecting the modifications in host metabolism elicited by viral infections. Up until the present, only a single omics study has been conducted by MS that explores the interaction between the host and CCHFV and the ensuing pathogenesis (12). NMR and MS are the two commonly utilized methods used for metabolomics studies with each having certain strengths and weaknesses depending on their purpose of use.…”

“…So far there is only one omics study which investigates host-viral response and pathogenesis of CCHF utilizing transcriptomics and proteomics methods (12). Led by this gap in the literature, we conducted a nationwide analysis of metabolomes of patients hospitalized due to CCHF.…”