1. Longitudinal blood cell transcriptomic profiling and in vitro temporal proteomics provides novel insights into metabolic reprogramming and host-immune responses against Crimean-Congo Hemorrhagic Fever Virus
- Author
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Friedemann Weber, Binnur Bagci, Soham Gupta, Vegvari A, Banerjea A, Emma Kennedy, Anoop T. Ambikan, Sofia Appelberg, Dowall S, Roger Hewson, Monteil, Akusjärvi Ss, Rodriguez J, Ali Mirazimi, Neogi U, and Nazif Elaldi more...
- Subjects
Transcriptome ,Blood cell ,Immune system ,medicine.anatomical_structure ,Host (biology) ,Metabolic reprogramming ,medicine ,Biology ,Proteomics ,Virology ,Crimean Congo hemorrhagic fever virus ,In vitro - Abstract
The pathogenesis and host-viral interactions of the Crimean–Congo hemorrhagic fever orthonairovirus (CCHFV) are convoluted and is not well evaluated. 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 the infection and temporal untargeted proteomics analysis of CCHFV infected Huh7 cells. Our results indicate that during the acute phase of CCHFV infection, the host's metabolic reprogramming towards central carbon metabolism including glycolysis and glutaminolysis occurs that favours the virus replication as blocking these pathways in vitro inhibits CCHFV cellular replication. Furthermore, CCHFV replication was inhibited by blocking Akt with MK-2206 suggesting a regulatory role of PI3K/Akt/mTOR pathways. We also show activation of key interferon stimulating genes during infection, suggesting a role for type I and II interferon-mediated antiviral mechanisms. Targeting immune-metabolic pathways could be attractive therapeutic intervention for CCHFV. more...
- Published
- 2021
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