التفاصيل البيبلوغرافية
| العنوان: |
Multi-omics Insights Into Host-viral Response and Pathogenesis in Crimean-Congo Hemorrhagic Fever Viruses for Novel Therapeutic Target. |
| المؤلفون: |
Neogi, Ujjwal1, Elaldı, Nazif1, Appelberg, Sofia1, Ambikan, Anoop T.1, Kennedy, Emma1, Dowall, Stuart1, Bağcı, Binnur Köksal1, Gupta, Soham1, Rodriguez, Jimmy E.1, Akusjärvi, Sara Svensson1, Monteil, Vanessa V.1, Végvári, Ákos1, Benfeitas, Rui1, Çömez, Ayşenur1, Hewson, Roger1, Mirazimi, Ali1 |
| المصدر: |
Mediterranean Journal of Infection, Microbes & Antimicrobials. 2022 Supplement, Vol. 11, p289-290. 2p. |
| مستخلص: |
Objectives: The pathogenesis and host-viral interactions of the CrimeanCongo hemorrhagic fever orthonairovirus (CCHFV) are convoluted and not well evaluated. Application of the multiomics system biology approaches including biological network analysis in elucidating the complex host-viral response, allow for interrogating the viral pathogenesis. The present study aimed to fingerprint the system-level alterations during acute CCHFV-infection and the cellular immune responses during productive CCHFVreplication in vitro. Materials and Methods: Hospitalized CCHF patients between 2017 and 2018 at Sivas Cumhuriyet University Hospital, Turkey were recruited. Eighteen acute stage of PBMC samples were collected with a medyan time of 4 days (range 1-6 days) after the onset of symptoms. The convalescent stage of PBMC samples were also collected from 12 patients after one year. Here, we have applied global blood transcriptomics to measure the system-wide changes during the CCHFV-infection and temporal quantitative proteomics analysis to understand the cellular alterations during the productive CCHFV-infection in two different cell lines, human adrenal carcinoma cell line, SW13 and human liver cell line Huh7 that were reported to be the most permissive cell lines for CCHFV. Results: In the RNAseq analysis of the PBMCs, comparing the acute and convalescent-phase, we observed system-level host’s metabolic reprogramming towards central carbon and energy metabolism (CCEM) with distinct upregulation of oxidative phosphorylation (OXPHOS) during CCHFV-infection. Upon application of network-based system biology methods, negative coordination of the biological signaling systems like FOXO/Notch axis and Akt/mTOR/HIF-1 signaling with metabolic pathways during CCHFV-infection were observed. The temporal quantitative proteomics in Huh7 showed a dynamic change in the CCEM over time and was in agreement with the cross-sectional proteomics in SW13 cells. By blocking the two key CCEM pathways, glycolysis and glutaminolysis, viral replication was inhibited in vitro. Conclusion: Activation of key interferon stimulating genes during CCHF suggested the role of type I and II interferon mediated antiviral mechanisms both at system-level and during progressive replication. Our study thus provides a comprehensive, system-level picture of the regulation of cellular and metabolic pathways during productive CCHFV-infection that can aid to identify novel therapeutic targets and strategies. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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