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Review

Molecular and Cellular Microbiology (MCM)  |  Host-Microbe Interactions and Pathogenesis

Understanding Metabolic Pathway Rewiring by Oncogenic Gamma Herpesvirus

Un Yung Choi1,2* and Seung Hyun Lee1,2

1Department of Microbiology, Konkuk University School of Medicine, Chungju 27478, Republic of Korea
2KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine, Chungju 27478, Republic of Korea

Correspondence to:
Un Yung Choi,       uychoi@kku.ac.kr
Received: July 22, 2024; Revised: August 14, 2024; Accepted: August 19, 2024

J. Microbiol. Biotechnol. 2024; 34(11): 2143-2152

Published November 28, 2024 https://doi.org/10.4014/jmb.2407.07039

Copyright © The Korean Society for Microbiology and Biotechnology.

Abstract

Gamma herpesviruses, including Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV), are key contributors to the development of various cancers through their ability to manipulate host cellular pathways. This review explores the intricate ways these viruses rewire host metabolic pathways to sustain viral persistence and promote tumorigenesis. We look into how EBV and KSHV induce glycolytic reprogramming, alter mitochondrial function, and remodel nucleotide and amino acid metabolism, highlighting the crucial role of lipid metabolism in these oncogenic processes. By understanding these metabolic alterations, which confer proliferative and survival advantages to the virus-infected cells, we can identify potential therapeutic targets and develop innovative treatment strategies for gamma herpesvirus-associated malignancies. Ultimately, this review underscores the critical role of metabolic reprogramming in gamma herpesvirus oncogenesis and its implications for precision medicine in combating virus-driven cancers.

Keywords

Metabolic reprogramming, EBV, KSHV, oncogenic virus, metabolic therapeutics

Graphical Abstract


References

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Article

Review

J. Microbiol. Biotechnol. 2024; 34(11): 2143-2152

Published online November 28, 2024 https://doi.org/10.4014/jmb.2407.07039

Copyright © The Korean Society for Microbiology and Biotechnology.

Understanding Metabolic Pathway Rewiring by Oncogenic Gamma Herpesvirus

Un Yung Choi1,2* and Seung Hyun Lee1,2

1Department of Microbiology, Konkuk University School of Medicine, Chungju 27478, Republic of Korea
2KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine, Chungju 27478, Republic of Korea

Correspondence to:Un Yung Choi,       uychoi@kku.ac.kr

Received: July 22, 2024; Revised: August 14, 2024; Accepted: August 19, 2024

Abstract

Gamma herpesviruses, including Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV), are key contributors to the development of various cancers through their ability to manipulate host cellular pathways. This review explores the intricate ways these viruses rewire host metabolic pathways to sustain viral persistence and promote tumorigenesis. We look into how EBV and KSHV induce glycolytic reprogramming, alter mitochondrial function, and remodel nucleotide and amino acid metabolism, highlighting the crucial role of lipid metabolism in these oncogenic processes. By understanding these metabolic alterations, which confer proliferative and survival advantages to the virus-infected cells, we can identify potential therapeutic targets and develop innovative treatment strategies for gamma herpesvirus-associated malignancies. Ultimately, this review underscores the critical role of metabolic reprogramming in gamma herpesvirus oncogenesis and its implications for precision medicine in combating virus-driven cancers.

Keywords: Metabolic reprogramming, EBV, KSHV, oncogenic virus, metabolic therapeutics

References

  1. Butel JS. 2000. Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease. Carcinogenesis 21: 405-426.
    Pubmed
  2. Jha HC, Banerjee S, Robertson ES. 2016. The role of gammaherpesviruses in cancer pathogenesis. Pathogens 5: 18.
    Pubmed KoreaMed
  3. Wen KW, Wang L, Menke JR, Damania B. 2022. Cancers associated with human gammaherpesviruses. FEBS J. 289: 7631-7669.
    Pubmed KoreaMed
  4. Kim ET, Kim KD. 2022. Topological implications of DNA tumor viral episomes. BMB Rep. 55: 587-594.
    Pubmed KoreaMed
  5. Lo AK, Dawson CW, Young LS, Lo KW. 2017. The role of metabolic reprogramming in gamma-herpesvirus-associated oncogenesis. Int. J. Cancer 141: 1512-1521.
    Pubmed
  6. Speck SH, Ganem D. 2010. Viral latency and its regulation: lessons from the gamma-herpesviruses. Cell Host Microbe 8: 100-115.
    Pubmed KoreaMed
  7. Sorel O, Dewals BG. 2018. The critical role of genome maintenance proteins in immune evasion during gammaherpesvirus latency. Front. Microbiol. 9: 3315.
    Pubmed KoreaMed
  8. Yan L, Majerciak V, Zheng ZM, Lan K. 2019. Towards better understanding of KSHV life cycle: from transcription and posttranscriptional regulations to pathogenesis. Virol. Sin. 34: 135-161.
    Pubmed KoreaMed
  9. Kempkes B, Robertson ES. 2015. Epstein-Barr virus latency: current and future perspectives. Curr. Opin. Virol. 14: 138-144.
    Pubmed KoreaMed
  10. Yang J, Liu Z, Zeng B, Hu G, Gan R. 2020. Epstein-Barr virus-associated gastric cancer: a distinct subtype. Cancer Lett. 495: 191-199.
    Pubmed
  11. Traylen CM, Patel HR, Fondaw W, Mahatme S, Williams JF, Walker LR, et al. 2011. Virus reactivation: a panoramic view in human infections. Future Virol. 6: 451-463.
    Pubmed KoreaMed
  12. Dubich T, Dittrich A, Bousset K, Geffers R, Busche G, Koster M, et al. 2021. 3D culture conditions support Kaposi's sarcoma herpesvirus (KSHV) maintenance and viral spread in endothelial cells. J. Mol. Med (Berl) 99: 425-438.
    Pubmed KoreaMed
  13. Guo R, Liang JH, Zhang Y, Lutchenkov M, Li Z, Wang Y, et al. 2022. Methionine metabolism controls the B cell EBV epigenome and viral latency. Cell Metab. 34: 1280-1297 e1289.
    Pubmed KoreaMed
  14. Damania B, Kenney SC, Raab-Traub N. 2022. Epstein-Barr virus: biology and clinical disease. Cell 185: 3652-3670.
    Pubmed KoreaMed
  15. Luo Y, Liu Y, Wang C, Gan R. 2021. Signaling pathways of EBV-induced oncogenesis. Cancer Cell Int. 21: 93.
    Pubmed KoreaMed
  16. Cesarman E, Damania B, Krown SE, Martin J, Bower M, Whitby D. 2019. Kaposi sarcoma. Nat. Rev. Dis. Primers 5: 9.
    Pubmed KoreaMed
  17. Privatt SR, Braga CP, Johnson A, Lidenge SJ, Berry L, Ngowi JR, et al. 2023. Comparative polar and lipid plasma metabolomics differentiate KSHV infection and disease states. Cancer Metab. 11: 13.
    Pubmed KoreaMed
  18. Hegedus A, Kavanagh Williamson M, Khan MB, Dias Zeidler J, Da Poian AT, El-Bacha T, et al. 2017. Evidence for altered glutamine metabolism in human immunodeficiency virus type 1 infected primary human CD4+ T cells. AIDS Res. Hum. Retroviruses 33: 12361247.
    Pubmed KoreaMed
  19. Thakker S, Verma SC. 2016. Co-infections and Pathogenesis of KSHV-Associated Malignancies. Front. Microbiol. 7: 151.
    Pubmed KoreaMed
  20. Vander Heiden MG, Cantley LC, Thompson CB. 2009. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324: 1029-1033.
    Pubmed KoreaMed
  21. Liberti MV, Locasale JW. 2016. The warburg effect: how does it benefit cancer cells? Trends Biochem. Sci. 41: 211-218.
    Pubmed KoreaMed
  22. Wang ZH, Peng WB, Zhang P, Yang XP, Zhou Q. 2021. Lactate in the tumour microenvironment: from immune modulation to therapy. EBioMedicine 73: 103627.
    Pubmed KoreaMed
  23. Chen Z, Han F, Du Y, Shi H, Zhou W. 2023. Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions. Signal Transduct. Target. Ther. 8: 70.
    Pubmed KoreaMed
  24. Raimundo N, Baysal BE, Shadel GS. 2011. Revisiting the TCA cycle: signaling to tumor formation. Trends Mol. Med. 17: 641-649.
    Pubmed KoreaMed
  25. Tarrado-Castellarnau M, de Atauri P, Cascante M. 2016. Oncogenic regulation of tumor metabolic reprogramming. Oncotarget 7: 62726-62753.
    Pubmed KoreaMed
  26. Keibler MA, Wasylenko TM, Kelleher JK, Iliopoulos O, Vander Heiden MG, Stephanopoulos G. 2016. Metabolic requirements for cancer cell proliferation. Cancer Metab. 4: 16.
    Pubmed KoreaMed
  27. Koundouros N, Poulogiannis G. 2020. Reprogramming of fatty acid metabolism in cancer. Br. J. Cancer 122: 4-22.
    Pubmed KoreaMed
  28. Bosc C, Broin N, Fanjul M, Saland E, Farge T, Courdy C, et al. 2020. Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites. Nat. Commun. 11: 4056.
    Pubmed KoreaMed
  29. Poillet-Perez L, Xie X, Zhan L, Yang Y, Sharp DW, Hu ZS, et al. 2018. Autophagy maintains tumour growth through circulating arginine. Nature 563: 569-573.
    Pubmed KoreaMed
  30. Commisso C, Davidson SM, Soydaner-Azeloglu RG, Parker SJ, Kamphorst JJ, Hackett S, et al. 2013. Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 497: 633-637.
    Pubmed KoreaMed
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