Human Monocytes - CD14, CD16 - Ziegler-Heitbrock

Contact

Metabolic perturbation associated with COVID-19 disease severity and SARS-CoV-2 replication.

Abstract

Viruses hijack host metabolic pathways for their replicative advantage. In this study, using patient-derived multi-omics 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 (SARS-CoV-2) reproduction and their association with disease severity. We used multi-omics 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 to understand viral-induced metabolic modulations. We also modulated key metabolic pathways that were identified using multi-omics data to regulate the viral reproduction in vitro. COVID-19 disease severity was characterized by increased plasma glucose and mannose levels. Immune phenotyping identified altered expression patterns of carbohydrate transporter, GLUT1, in CD8+ T-cells, intermediate and non-classical monocytes, and amino acid transporter, xCT, in classical, intermediate, and non-classical 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 SARS-CoV-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.

Authors: Krishnan S, Nordqvist H, Ambikan AT, Gupta S, Sperk M, Svensson-Akusjärvi S, Mikaeloff F, Benfeitas R, Saccon E, Ponnan SM, Rodriguez JE, Nikouyan N, Odeh A, Ahlén G, Asghar M, Sällberg M, Vesterbacka J, Nowak P, Végvári Á, Sönnerborg A, Treutiger CJ, Neo
Journal: Mol Cell Proteomics;2021Oct04 100159. doi:10.1016/j.mcpro.2021.100159
Year: 2021
PubMed: PMID: 34619366 (Go to PubMed)