Systemic metabolic changes in acute and chronic lymphocytic choriomeningitis virus infection Journal Article
| Authors: | Bartman, C. R.; Hou, S.; Correa, F.; Shen, Y.; da Silva-Diz, V.; Aleksandrova, M.; Herranz, D.; Rabinowitz, J. D.; Intlekofer, A. M. |
| Article Title: | Systemic metabolic changes in acute and chronic lymphocytic choriomeningitis virus infection |
| Abstract: | Objective: Viral infection of cells leads to metabolic changes, but how viral infection changes whole-body and tissue metabolism in vivo has not been comprehensively studied. In particular, it is unknown how metabolism might be differentially affected by an acute infection that the immune system can successfully clear compared to a chronic persistent infection. Methods: Here we used metabolomics and isotope tracing to identify metabolic changes in mice infected with acute or chronic forms of lymphocytic choriomeningitis virus (LCMV) for three or eight days. Results: Both types of infection alter metabolite levels in blood and tissues, including itaconate and thymidine. However, we observed more dramatic metabolite changes in the blood and tissues of mice with persisting LCMV infection compared to those infected with the acute viral strain. Isotope tracing revealed that the contribution of both glucose and glutamine to the tricarboxylic acid (TCA) cycle increase in the spleen, liver, and kidneys of mice infected with chronic LCMV, while acute LCMV only increases the contribution of glutamine to the TCA cycle in the spleen. We found that whole-body turnover of both glutamine and thymidine increase during acute and chronic infection, whereas whole-body glucose turnover surprisingly does not change. Activated T cells in vitro produce thymidine and virus-specific T cells ex vivo have increased thymidine levels, nominating T lymphocytes as the source of thymidine in LCMV infection. Conclusions: In sum, we provide comprehensive measurements of whole-body and tissue metabolism in acute and chronic viral infection, and identify altered thymidine metabolism as a marker of viral infection. © 2025 The Authors |
| Keywords: | nonhuman; t lymphocyte; animal cell; mouse; metabolism; animal tissue; spleen; protein metabolism; animal experiment; animal model; blood analysis; glucose; ex vivo study; virus strain; metabolite; t lymphocyte activation; glutamine; citric acid cycle; metabolomics; lymphocytic choriomeningitis; lymphocytic choriomeningitis virus; amino acid synthesis; isotope tracing; tissue metabolism; tricarboxylic acid; article; kidney tissue; immunometabolism; liver tissue; itaconic acid; doxribtimine; whole-body metabolism |
| Journal Title: | Molecular Metabolism |
| Volume: | 99 |
| ISSN: | 2212-8778 |
| Publisher: | Elsevier BV |
| Date Published: | 2025-08-31 |
| Start Page: | 102194 |
| Language: | English |
| DOI: | 10.1016/j.molmet.2025.102194 |
| PUBMED: | 40581045 |
| PROVIDER: | scopus |
| PMCID: | PMC12274302 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Andrew M. Intlekofer -- Source: Scopus |
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