Krishnan, S and Nordqvist, H and Ambikan, AT and Gupta, S and Sperk, M and Svensson-Akusjärvi, S and Mikaeloff, F and Benfeitas, R and Saccon, E and Ponnan, SM and Rodriguez, JE and Nikouyan, N and Odeh, A and Ahlén, G and Asghar, M and Sällberg, M and Vesterbacka, J and Nowak, P and Végvári, � and Sönnerborg, A and Treutiger, CJ and Neogi, U (2021) Metabolic perturbation associated with COVID-19 disease severity and SARS-CoV-2 replication. In: Molecular and Cellular Proteomics, 20 .
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Abstract
Viruses hijack host metabolic pathways for their replicative advantage. In this study, using patient-derived multiomics data and in vitro infection assays, we aimed to understand the role of key metabolic pathways that can regulate severe acute respiratory syndrome coronavirus-2 reproduction and their association with disease severity. We used multiomics platforms (targeted and untargeted proteomics and untargeted metabolomics) on patient samples and cell-line models along with immune phenotyping of metabolite transporters in patient blood cells to understand viral-induced metabolic modulations. We also modulated key metabolic pathways that were identified using multiomics data to regulate the viral reproduction in vitro. Coronavirus disease 2019 disease severity was characterized by increased plasma glucose and mannose levels. Immune phenotyping identified altered expression patterns of carbohydrate transporter, glucose transporter 1, in CD8+ T cells, intermediate and nonclassical monocytes, and amino acid transporter, xCT, in classical, intermediate, and nonclassical monocytes. In in vitro lung epithelial cell (Calu-3) infection model, we found that glycolysis and glutaminolysis are essential for virus replication, and blocking these metabolic pathways caused significant reduction in virus production. Taken together, we therefore hypothesized that severe acute respiratory syndrome coronavirus-2 utilizes and rewires pathways governing central carbon metabolism leading to the efflux of toxic metabolites and associated with disease severity. Thus, the host metabolic perturbation could be an attractive strategy to limit the viral replication and disease severity.
| Item Type: | Journal Article |
|---|---|
| Publication: | Molecular and Cellular Proteomics |
| Publisher: | American Society for Biochemistry and Molecular Biology Inc. |
| Additional Information: | The copyright for this article belongs to the Author. |
| Keywords: | Adult; Aged; Amino Acid Transport System y+; Amino Acids; Biomarkers; Blood Proteins; Carbohydrates; Case-Control Studies; COVID-19; Glucose Transporter Type 1; Hospitalization; Humans; Immunophenotyping; Mannose; Mannose-Binding Lectin; Middle Aged; SARS-CoV-2; Severity of Illness Index; Virus Replication amino acid transporter; angiopoietin 2; CXCL13 chemokine; Fas ligand; glucose; glucose transporter 1; interleukin 12; mannose; monocyte chemotactic protein 3; plasma protein; pleiotrophin; scatter factor; SLC7A11 protein; stromal cell derived factor 1; tumor necrosis factor; unclassified drug; vasculotropin A; amino acid; amino acid transporter; biological marker; carbohydrate; glucose transporter 1; mannose; mannose binding lectin; plasma protein; SLC2A1 protein, human; SLC7A11 protein, human adult; Article; blood cell; Calu-3 cell line; CD8+ T lymphocyte; cell population; clinical article; controlled study; coronavirus disease 2019; disease severity; female; glucose blood level; glycolysis; human; human cell; immunophenotyping; in vitro study; male; metabolic regulation; metabolism; metabolite; metabolomics; monocyte; multiomics; nonhuman; protein expression; proteomics; quantitative analysis; Severe acute respiratory syndrome coronavirus 2; virus replication; aged; blood; case control study; etiology; hospitalization; middle aged; physiology; severity of illness index; virology; virus replication |
| Department/Centre: | Division of Biological Sciences > Centre for Infectious Disease Research |
| Date Deposited: | 02 May 2023 09:04 |
| Last Modified: | 02 May 2023 09:04 |
| URI: | https://eprints.iisc.ac.in/id/eprint/81467 |
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