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Review
. 2022 Mar 14;14(3):602.
doi: 10.3390/v14030602.

Hallmarks of Metabolic Reprogramming and Their Role in Viral Pathogenesis

Charles N S Allen  1 , Sterling P Arjona  1 , Maryline Santerre  1 , Bassel E Sawaya  1   2   3   4
Affiliations
Review

Hallmarks of Metabolic Reprogramming and Their Role in Viral Pathogenesis

Charles N S Allen et al. Viruses. .

Abstract

Metabolic reprogramming is a hallmark of cancer and has proven to be critical in viral infections. Metabolic reprogramming provides the cell with energy and biomass for large-scale biosynthesis. Based on studies of the cellular changes that contribute to metabolic reprogramming, seven main hallmarks can be identified: (1) increased glycolysis and lactic acid, (2) increased glutaminolysis, (3) increased pentose phosphate pathway, (4) mitochondrial changes, (5) increased lipid metabolism, (6) changes in amino acid metabolism, and (7) changes in other biosynthetic and bioenergetic pathways. Viruses depend on metabolic reprogramming to increase biomass to fuel viral genome replication and production of new virions. Viruses take advantage of the non-metabolic effects of metabolic reprogramming, creating an anti-apoptotic environment and evading the immune system. Other non-metabolic effects can negatively affect cellular function. Understanding the role metabolic reprogramming plays in viral pathogenesis may provide better therapeutic targets for antivirals.

Keywords: Warburg effect; amino acid metabolism; biomass; biosynthetic and bioenergetic pathways; glutaminolysis; glycolysis; lipid metabolism; metabolic reprogramming; mitochondria; pentose phosphate pathway; viral replication; virus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Hallmarks of metabolic reprogramming. The illustration represents the seven hallmarks of metabolic reprogramming: 1—increased glycolysis, 2—increased glutaminolysis, 3—increased pentose phosphate pathway, 4—mitochondrial changes and TCA rewiring, 5—increased lipid metabolism, 6—changes in amino acid metabolism, and 7—changes in other biosynthetic and bioenergetic pathways.
Figure 2
Figure 2
Glycolysis and the pentose phosphate pathway in metabolic reprogramming. (A) Upregulated glycolysis in metabolic reprogramming including the transcriptional regulation and increased expression of glucose transporters as well as the consequences of increased glycolysis. (B) Mechanisms leading to pentose phosphate pathway (PPP) upregulation during metabolic reprogramming include both branches and transcriptional regulation of critical enzymes.
Figure 3
Figure 3
Glutaminolysis, mitochondrial changes, lipid metabolism, and amino acid metabolism in metabolic reprogramming. (A) Upregulation of glutaminolysis via transcriptional regulation and the status of miR-23. The cartoon also displays an increased expression of glutamine transporters and enzymes. (B) A schematic representation of mitochondrial rewiring of the TCA cycle during metabolic reprogramming includes transporting key TCA metabolites outside the mitochondria and the transcriptional regulation of critical enzymes and transporters. (C) Increased lipid metabolism, ROS, and the transportation of citrate out of the mitochondria used for lipid synthesis as a part of metabolic reprogramming. (D) Amino acid metabolism regulation in metabolic reprogramming includes the increase in certain amino acids that act as precursors for others.
Figure 4
Figure 4
Non-metabolic effects of metabolic reprogramming. The cartoon shows how the seven hallmarks of metabolic reprogramming led to non-metabolic effects: inflammation, anti-apoptosis, immune evasion, and production of advanced glycation end products.
Figure 5
Figure 5
Formation of the advanced glycation end products. The illustration displays two pathways: Maillard reactions and the spontaneous degradation of glycolysis intermediates that lead to the formation of three types of advanced glycation end products.
See this image and copyright information in PMC

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References

    1. Medina M.Á. Metabolic Reprogramming is a Hallmark of Metabolism Itself. Bioessays. 2020;42:e2000058. doi: 10.1002/bies.202000058. - DOI - PubMed
    1. Warburg O., Posener K., Negelein E. Ueber den Stoffwechsel der Tumoren. Biochem. Z. 1924;152:319–344. (In German). Reprinted in English in the book On metabolism of tumors by O. Warburg, Publisher: Constable, London, 1930.
    1. Liberti M.V., Locasale J.W. The Warburg Effect: How Does it Benefit Cancer Cells? Trends Biochem. Sci. 2016;41:211–218. doi: 10.1016/j.tibs.2015.12.001. - DOI - PMC - PubMed
    1. Vander Heiden M.G., Cantley L.C., Thompson C.B. Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science. 2009;324:1029–1033. doi: 10.1126/science.1160809. - DOI - PMC - PubMed
    1. Vaupel P., Schmidberger H., Mayer A. The Warburg effect: Essential part of metabolic reprogramming and central contributor to cancer progression. Int. J. Radiat. Biol. 2019;95:912–919. doi: 10.1080/09553002.2019.1589653. - DOI - PubMed

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