Related Experiment Video
Updated: Jun 9, 2026
An In Vitro Model for Measuring Immune Responses to Malaria in the Context of HIV Co-infection
Published on: October 6, 2015
Systems-level temporal immune-metabolic profile in Crimean-Congo hemorrhagic fever virus infection
Anoop T Ambikan1, Nazif Elaldi2, Sara Svensson-Akusjärvi1
1The Systems Virology Lab, Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, ANA Futura, Stockholm-14152, Sweden.
Insights
Crimean-Congo hemorrhagic fever (CCHF) pathogenesis involves immune signaling and metabolic shifts. Acute infection shows increased energy demand and amino acid metabolism, while the convalescent phase suggests metabolic rewiring and potential post-viral fatigue.
Area of Science:
- Virology
- Immunology
- Systems Biology
- Metabolomics
Background:
- Crimean-Congo hemorrhagic fever (CCHF) is a WHO-prioritized epidemic-prone disease requiring urgent research.
- The host response trajectory and pathogenesis of CCHF virus (CCHFV) infection are not fully understood.
Purpose of the Study:
- To elucidate the temporal spectrum of CCHF pathogenesis.
- To analyze immune-pathogenic alterations and metabolic shifts during CCHF infection.
Main Methods:
- Genome-wide blood transcriptomics and systems biology analysis.
- Development of context-specific genome-scale metabolic models (GSMM).
- Analysis of samples from acute, early convalescent, and convalescent phases (T0, T1, T2).
Main Results:
- Immune response trajectory governed by RIG-I-like/NOD-like receptor and TNF signaling.
- Acute CCHFV infection shows metabolic shifts towards amino acid metabolism, oxidative phosphorylation, and fatty acid oxidation.
- Upregulation of TCA cycle, glycolysis, and pyruvate metabolism indicates increased energy demand and cellular stress during acute infection.
Conclusions:
- Metabolic alterations, including TCA cycle and glycolysis upregulation, are key to CCHF pathogenicity.
- Downregulation of metabolic processes in the convalescent phase may lead to metabolic rewiring and post-viral fatigue syndrome.
Abstract:
Crimean-Congo hemorrhagic fever (CCHF) caused by CCHF virus (CCHFV) is one of the epidemic-prone diseases prioritized by the World Health Organisation as public health emergency with an urgent need for accelerated research. The trajectory of host response against CCHFV is multifarious and remains unknown. Here, we reported the temporal spectrum of pathogenesis following the CCHFV infection using genome-wide blood transcriptomics analysis followed by advanced systems biology analysis, temporal immune-pathogenic alterations, and context-specific progressive and postinfection genome-scale metabolic models (GSMM) on samples collected during the acute (T0), early convalescent (T1), and convalescent-phase (T2). The interplay between the retinoic acid-inducible gene-I-like/nucleotide-binding oligomerization domain-like receptor and tumor necrosis factor signaling governed the trajectory of antiviral immune responses. The rearrangement of intracellular metabolic fluxes toward the amino acid metabolism and metabolic shift toward oxidative phosphorylation and fatty acid oxidation during acute CCHFV infection determine the pathogenicity. The upregulation of the tricarboxylic acid cycle during CCHFV infection, compared to the noninfected healthy control and between the severity groups, indicated an increased energy demand and cellular stress. The upregulation of glycolysis and pyruvate metabolism potentiated energy generation through alternative pathways associated with the severity of the infection. The downregulation of metabolic processes at the convalescent phase identified by blood cell transcriptomics and single-cell type proteomics of five immune cells (CD4+ and CD8+ T cells, CD14+ monocytes, B cells, and NK cells) potentially leads to metabolic rewiring through the recovery due to hyperactivity during the acute phase leading to post-viral fatigue syndrome.
