Analysis of temporal metabolic rewiring for human respiratory syncytial virus infection by integrating metabolomics and proteomics.

Publisher: Springer Country of Publication: United States NLM ID: 101274889 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-3890 (Electronic) Linking ISSN: 15733882 NLM ISO Abbreviation: Metabolomics Subsets: MEDLINE

Original Publication: New York : Springer, c2006-

Respiratory Syncytial Virus Infections*/metabolism ; Respiratory Syncytial Virus, Human*/genetics; Animals ; Mice ; Humans ; Proteomics ; Metabolomics ; Epithelial Cells/metabolism

Introduction: Human respiratory syncytial virus (HRSV) infection causes significant morbidity, and no effective treatments are currently available. Viral infections induce substantial metabolic changes in the infected cells to optimize viral production. Metabolites that reflect the interactions between host cells and viruses provided an opportunity to identify the pathways underlying severe infections.
Objective: To better understand the metabolic changes caused by HRSV infection, we analyzed temporal metabolic profiling to provide novel targets for therapeutic strategies for inhaled HRSV infection.
Methods: The epithelial cells and BALB/c mice were infected with HRSV. Protein and mRNA levels of inflammation factors were measured by using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Untargeted metabolomics, lipidomics and proteomics were performed using liquid chromatography coupled with mass spectrometry to profile the metabolic phenotypic alterations in HRSV infection.
Results: In this study, we evaluated the inflammatory responses in vivo and in vitro and investigated the temporal metabolic rewiring of HRSV infection in epithelial cells. We combined metabolomics and proteomic analyses to demonstrate that the redox imbalance was further provoked by increasing glycolysis and anaplerotic reactions. These responses created an oxidant-rich microenvironment that elevated reactive oxygen species levels and exacerbated glutathione consumption.
Conclusion: These observations indicate that adjusting for metabolic events during a viral infection could represent a valuable approach for reshaping the outcome of infections.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cytogenet Cell Genet. 1988;48(1):19-24. (PMID: 3180844)
Nat Rev Mol Cell Biol. 2019 Jun;20(6):353-367. (PMID: 30814649)
Nat Biotechnol. 2021 Nov;39(11):1375-1384. (PMID: 34083791)
Physiol Rev. 2020 Jan 1;100(1):171-210. (PMID: 31487233)
Viruses. 2022 Mar 14;14(3):. (PMID: 35337009)
Nature. 2021 Jun;594(7862):246-252. (PMID: 33845483)
Nat Biotechnol. 2016 Aug 9;34(8):828-837. (PMID: 27504778)
mBio. 2021 Oct 26;12(5):e0063521. (PMID: 34517756)
Exp Mol Med. 2020 Sep;52(9):1496-1516. (PMID: 32943735)
PLoS One. 2020 Mar 26;15(3):e0230844. (PMID: 32214395)
Pathogens. 2021 Dec 26;11(1):. (PMID: 35055974)
Nat Rev Gastroenterol Hepatol. 2021 Dec;18(12):835-856. (PMID: 34508238)
Nat Rev Genet. 2013 Jan;14(1):35-48. (PMID: 23207911)
Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6663-6674. (PMID: 32139610)
Annu Rev Biomed Eng. 2017 Jun 21;19:163-194. (PMID: 28301735)
J Gen Virol. 2017 Dec;98(12):2912-2913. (PMID: 29087278)
Viruses. 2021 Oct 13;13(10):. (PMID: 34696488)
Adv Sci (Weinh). 2021 Sep;8(17):e2101222. (PMID: 34180141)
Cell. 2018 Sep 6;174(6):1571-1585.e11. (PMID: 30193114)
Nat Rev Genet. 2012 Mar 13;13(4):227-32. (PMID: 22411467)
Sci Rep. 2017 Nov 6;7(1):14567. (PMID: 29109515)
Cell Mol Life Sci. 2020 Dec;77(24):5045-5058. (PMID: 32556372)
Cell Mol Biol Lett. 2020 Mar 5;25:15. (PMID: 32161622)
J Virol. 2018 Jul 17;92(15):. (PMID: 29769339)
Signal Transduct Target Ther. 2020 May 29;5(1):84. (PMID: 32467561)
Biochimie. 2021 Jan;180:169-177. (PMID: 33189832)
Antioxid Redox Signal. 2021 May 10;34(14):1069-1082. (PMID: 33270507)
Environ Sci Technol. 2021 Apr 20;55(8):5097-5105. (PMID: 33683876)
Lancet. 2010 May 1;375(9725):1545-55. (PMID: 20399493)
Nat Commun. 2021 Jan 4;12(1):98. (PMID: 33397935)
Biochemistry (Mosc). 2021 Mar;86(3):290-306. (PMID: 33838630)
Chem Sci. 2020 Jan 8;11(9):2531-2557. (PMID: 33209251)
Nature. 2020 Mar;579(7797):123-129. (PMID: 32103176)
Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Feb;1865(2):158542. (PMID: 31672571)
Nat Commun. 2019 Jul 22;10(1):3273. (PMID: 31332169)
Sci Rep. 2018 Jan 10;8(1):387. (PMID: 29321591)
ACS Infect Dis. 2020 Aug 14;6(8):2130-2142. (PMID: 32633123)
Front Cell Infect Microbiol. 2019 Apr 18;9:95. (PMID: 31058096)
J Virol. 2022 Apr 13;96(7):e0190421. (PMID: 35285685)
Cytokine. 2018 Dec;112:52-62. (PMID: 29960669)

Keywords: Glutamine and glutamate metabolism; Human respiratory syncytial virus; Metabolic remodeling; Metabolomics

Date Created: 20230329 Date Completed: 20230331 Latest Revision: 20230424

20240628

PMC10057675

10.1007/s11306-023-01991-2

36991292