본문 바로가기
KERD
논문KCI 등재

Understanding Metabolic Pathway Rewiring by Oncogenic Gamma Herpesvirus

1

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류생물학

초록

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.

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.

참고문헌 (81)

  1. Butel JS, "Viral carcinogenesis : revelation of molecular mechanisms and etiology of human disease", Carcinogenesis, 21, pp.405~426 (2000)
  2. Jha HC, "The role of gammaherpesviruses in cancer pathogenesis", Pathogens, 5, pp.18~ (2016)
  3. Wen KW, "Cancers associated with human gammaherpesviruses", FEBS J, 289, pp.7631~7669 (2022)
  4. Kim ET, "Topological implications of DNA tumor viral episomes", BMB Rep, 55, pp.587~594 (2022)
  5. Lo AK, "The role of metabolic reprogramming in gamma-herpesvirus-associated oncogenesis", Int. J. Cancer, 141, pp.1512~1521 (2017)
  6. Speck SH, "Viral latency and its regulation : lessons from the gamma-herpesviruses", Cell Host Microbe, 8, pp.100~115 (2010)
  7. Sorel O, "The critical role of genome maintenance proteins in immune evasion during gammaherpesvirus latency", Front. Microbiol, 9, pp.3315~ (2018)
  8. Yan L, "Towards better understanding of KSHV life cycle : from transcription and posttranscriptional regulations to pathogenesis", Virol. Sin, 34, pp.135~161 (2019)
  9. Kempkes B, "Epstein-Barr virus latency : current and future perspectives", Curr. Opin. Virol, 14, pp.138~144 (2015)
  10. Yang J, "Epstein-Barr virus-associated gastric cancer : a distinct subtype", Cancer Lett, 495, pp.191~199 (2020)
  11. Traylen CM, "Virus reactivation : a panoramic view in human infections", Future Virol, 6, pp.451~463 (2011)
  12. Dubich T, "3D culture conditions support Kaposi's sarcoma herpesvirus(KSHV)maintenance and viral spread in endothelial cells", J. Mol. Med(Berl), 99, pp.425~438 (2021)
  13. Guo R, "Methionine metabolism controls the B cell EBV epigenome and viral latency", Cell Metab, 34, pp.1280~1297 (2022)
  14. Damania B, "Epstein-Barr virus : biology and clinical disease", Cell, 185, pp.3652~3670 (2022)
  15. Luo Y, "Signaling pathways of EBV-induced oncogenesis", Cancer Cell Int, 21, pp.93~ (2021)
  16. Cesarman E, "Kaposi sarcoma", Nat. Rev. Dis. Primers, 5, pp.9~ (2019)
  17. Privatt SR, "Comparative polar and lipid plasma metabolomics differentiate KSHV infection and disease states", Cancer Metab, 11, pp.13~ (2023)
  18. Hegedus A, "Evidence for altered glutamine metabolism in human immunodeficiency virus type 1 infected primary human CD4+ T cells", AIDS Res. Hum. Retroviruses, 33, pp.1236~1247 (2017)
  19. Thakker S, "Co-infections and Pathogenesis of KSHV-Associated Malignancies", Front. Microbiol, 7, pp.151~ (2016)
  20. Vander Heiden MG, "Understanding the Warburg effect : the metabolic requirements of cell proliferation", Science, 324, pp.1029~1033 (2009)
  21. Liberti MV, "The warburg effect : how does it benefit cancer cells?", Trends Biochem. Sci, 41, pp.211~218 (2016)
  22. Wang ZH, "Lactate in the tumour microenvironment : from immune modulation to therapy", EBioMedicine, 73, pp.103627~ (2021)
  23. Chen Z, "Hypoxic microenvironment in cancer : molecular mechanisms and therapeutic interventions", Signal Transduct. Target. Ther, 8, pp.70~ (2023)
  24. Raimundo N, "Revisiting the TCA cycle : signaling to tumor formation", Trends Mol. Med, 17, pp.641~649 (2011)
  25. Tarrado-Castellarnau M, "Oncogenic regulation of tumor metabolic reprogramming", Oncotarget, 7, pp.62726~62753 (2016)
  26. Keibler MA, "Metabolic requirements for cancer cell proliferation", Cancer Metab, 4, pp.16~ (2016)
  27. Koundouros N, "Reprogramming of fatty acid metabolism in cancer", Br. J. Cancer, 122, pp.4~22 (2020)
  28. Bosc C, "Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites", Nat. Commun, 11, pp.4056~ (2020)
  29. Poillet-Perez L, "Autophagy maintains tumour growth through circulating arginine", Nature, 563, pp.569~573 (2018)
  30. Commisso C, "Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells", Nature, 497, pp.633~637 (2013)
  31. Sousa CM, "Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion", Nature, 536, pp.479~483 (2016)
  32. Duarte Mendes A, "Adipocyte microenvironment in ovarian cancer : a critical contributor?", Int. J. Mol. Sci, 24, pp.16589~ (2023)
  33. Galan-Cobo A, "LKB1 and KEAP1", NRF2 pathways cooperatively promote metabolic reprogramming with enhanced glutamine dependence in KRAS-mutant lung adenocarcinoma, 2019, pp.79, 3251~3267
  34. Xiang Y, "Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis", J. Clin. Invest, 125, pp.2293~2306 (2015)
  35. Yao K, "Synthetic lethality and synergetic effect : the effective strategies for therapy of IDH-mutated cancers", J. Exp. Clin. Cancer Res, 40, pp.263~ (2021)
  36. Zhang J, "Epstein-barr virus-encoded latent membrane protein 1 upregulates glucose transporter 1 transcription via the mTORC1", NF-kappaB signaling pathways, 2017, pp.91, e02168-16~
  37. Zhang J, "mTORC2-mediated PDHE1alpha nuclear translocation links EBV-LMP1reprogrammed glucose metabolism to cancer metastasis in nasopharyngeal carcinoma", Oncogene, 38, pp.4669~4684 (2019)
  38. Xiao L, "Targeting Epstein-Barr virus oncoprotein LMP1-mediated glycolysis sensitizes nasopharyngeal carcinoma to radiation therapy", Oncogene, 33, pp.4568~4578 (2014)
  39. Wolf A, "Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme", J. Exp. Med, 208, pp.313~326 (2011)
  40. Jiang Y, "Repression of Hox genes by LMP1 in nasopharyngeal carcinoma and modulation of glycolytic pathway genes by HoxC8", Oncogene, 34, pp.6079~6091 (2015)
  41. Delgado T, "Induction of the Warburg effect by Kaposi's sarcoma herpesvirus is required for the maintenance of latently infected endothelial cells", Proc. Natl. Acad. Sci. USA, 107, pp.10696~10701 (2010)
  42. Singh RK, "Metabolic reprogramming of Kaposi's sarcoma associated herpes virus infected B-cells in hypoxia", PLoS Pathog, 14, pp.e1007062~ (2018)
  43. Ma T, "KSHV induces aerobic glycolysis and angiogenesis through HIF-1-dependent upregulation of pyruvate kinase 2 in Kaposi's sarcoma", Angiogenesis, 18, pp.477~488 (2015)
  44. Qi X, "A viral interferon regulatory factor degrades RNA-binding protein hnRNP Q1 to enhance aerobic glycolysis via recruiting E3 ubiquitin ligase KLHL3 and decaying GDPD1 mRNA", Cell Death Differ, 29, pp.2233~2246 (2022)
  45. Zhu Y, "An oncogenic virus promotes cell survival and cellular transformation by suppressing glycolysis", PLoS Pathog, 12, pp.e1005648~ (2016)
  46. Luo X, "DNMT1 mediates metabolic reprogramming induced by Epstein-Barr virus latent membrane protein 1 and reversed by grifolin in nasopharyngeal carcinoma", Cell Death Dis, 9, pp.619~ (2018)
  47. Pal AD, "Epstein-Barr virus latent membrane protein-2A alters mitochondrial dynamics promoting cellular migration mediated by Notch signaling pathway", Carcinogenesis, 35, pp.1592~1601 (2014)
  48. Wang LW, "Epstein-barr-virus-induced one-carbon metabolism drives B cell transformation", Cell Metab, 30, pp.539~555 (2019)
  49. Holmes DL, "A CRISPR-Cas9 screen identifies mitochondrial translation as an essential process in latent KSHV infection of human endothelial cells", Proc. Natl. Acad. Sci. USA, 117, pp.28384~28392 (2020)
  50. Yogev O, "Kaposi's sarcoma herpesvirus microRNAs induce metabolic transformation of infected cells", PLoS Pathog, 10, pp.e1004400~ (2014)
  51. Vo MT, "Activation of NIX-mediated mitophagy by an interferon regulatory factor homologue of human herpesvirus", Nat. Commun, 10, pp.3203~ (2019)
  52. Liang JH, "Epstein-barr Virus Induced Cytidine Metabolism Roles in Transformed B-Cell Growth and Survival", mBio, 12, pp.e0153021~ (2021)
  53. Lee SW, "Overexpression of thymidylate synthetase confers an independent prognostic indicator in nasopharyngeal carcinoma", Exp. Mol. Pathol, 95, pp.83~90 (2013)
  54. Lamontagne RJ, "A multi-omics approach to Epstein-Barr virus immortalization of B-cells reveals EBNA1 chromatin pioneering activities targeting nucleotide metabolism", PLoS Pathog, 17, pp.e1009208~ (2021)
  55. Zhu Y, "A critical role of glutamine and asparagine gamma-Nitrogen in nucleotide biosynthesis in cancer cells Hijacked by an oncogenic virus", mBio, 8, pp.e01179-17~ (2017)
  56. Cinquina CC, "Dihydrofolate reductase from Kaposi's sarcoma-associated herpesvirus", Virology, 268, pp.201~217 (2000)
  57. Wan Q, "Hijacking of nucleotide biosynthesis and deamidation-mediated glycolysis by an oncogenic herpesvirus", Nat. Commun, 15, pp.1442~ (2024)
  58. Laurent C, "Several immune escape patterns in non-Hodgkin's lymphomas", Oncoimmunology, 4, pp.e1026530~ (2015)
  59. Raber P, "Metabolism of L-arginine by myeloid-derived suppressor cells in cancer : mechanisms of T cell suppression and therapeutic perspectives", Immunol. Invest, 41, pp.614~634 (2012)
  60. Liu WL, "Epstein-Barr virus infection induces indoleamine 2, 3-dioxygenase expression in human monocyte-derived macrophages through p38", mitogen-activated protein kinase and NF-kappaB pathways : impairment in T cell functions, 2014, pp.88, 6660~6671
  61. Guo D, "Expression of Tryptophan Metabolism Enzymes in Patients with Diffuse Large B-cell Lymphoma and NK", T-cell Lymphoma, 2023, pp.12, 12139~12148
  62. Chen X, "IDO, TDO, and AHR overexpression is associated with poor outcome in diffuse large B-cell lymphoma patients in the rituximab era", Medicine (Baltimore), 99, pp.e19883~ (2020)
  63. Ninomiya S, "Indoleamine 2, 3-dioxygenase in tumor tissue indicates prognosis in patients with diffuse large B-cell lymphoma treated with R-CHOP", Ann. Hematol, 90, pp.409~416 (2011)
  64. Sanchez EL, "Latent KSHV infected endothelial cells are glutamine addicted and require glutaminolysis for survival", PLoS Pathog, 11, pp.e1005052~ (2015)
  65. Valiya Veettil M, "Glutamate secretion and metabotropic glutamate receptor 1 expression during Kaposi's sarcoma-associated herpesvirus infection promotes cell proliferation", PLoS Pathog, 10, pp.e1004389~ (2014)
  66. Qin Z, "Upregulation of xCT by KSHV-encoded microRNAs facilitates KSHV dissemination and persistence in an environment of oxidative stress", PLoS Pathog, 6, pp.e1000742~ (2010)
  67. Dai L, "Targeting xCT, a cystine-glutamate transporter induces apoptosis and tumor regression for KSHV", HIV-associated lymphoma, 2014, pp.7, 30~
  68. Choi UY, "Oncogenic human herpesvirus hijacks proline metabolism for tumorigenesis", Proc. Natl. Acad. Sci. USA, 117, pp.8083~8093 (2020)
  69. Li Y, "Fatty acid synthase expression is induced by the Epstein-Barr virus immediate-early protein BRLF1 and is required for lytic viral gene expression", J. Virol, 78, pp.4197~4206 (2004)
  70. Daker M, "Deregulation of lipid metabolism pathway genes in nasopharyngeal carcinoma cells", Mol. Med. Rep, 7, pp.731~741 (2013)
  71. Lo AK, "Activation of sterol regulatory element-binding protein 1(SREBP1)-mediated lipogenesis by the Epstein-Barr virus-encoded latent membrane protein 1(LMP1)promotes cell proliferation and progression of nasopharyngeal carcinoma", J. Pathol, 246, pp.180~190 (2018)
  72. Wang LW, "Epstein-Barr virus subverts mevalonate and fatty acid pathways to promote infected B-cell proliferation and survival", PLoS Pathog, 15, pp.e1008030~ (2019)
  73. Feng J, "EBNA2 mediates lipid metabolism and tumorigenesis through activation of ATF4 pathway", Am. J. Cancer Res, 13, pp.1363~1376 (2023)
  74. Hulse M, "Epstein-Barr virus-encoded latent membrane protein 1 and B-cell growth transformation induce lipogenesis through fatty acid synthase", J. Virol, 95, pp.e01857-20~ (2021)
  75. Zheng S, "Downregulation of adipose triglyceride lipase by EB viralencoded LMP2A links lipid accumulation to increased migration in nasopharyngeal carcinoma", Mol. Oncol, 14, pp.3234~3252 (2020)
  76. Liu SC, "Epstein-Barr Virus induces adipocyte dedifferentiation to modulate the tumor microenvironment", Cancer Res, 81, pp.3283~3294 (2021)
  77. Sychev ZE, "Integrated systems biology analysis of KSHV latent infection reveals viral induction and reliance on peroxisome mediated lipid metabolism", PLoS Pathog, 13, pp.e1006256~ (2017)
  78. Tso FY, "RNA-Seq of Kaposi's sarcoma reveals alterations in glucose and lipid metabolism", PLoS Pathog, 14, pp.e1006844~ (2018)
  79. Delgado T, "Global metabolic profiling of infection by an oncogenic virus : KSHV induces and requires lipogenesis for survival of latent infection", PLoS Pathog, 8, pp.e1002866~ (2012)
  80. Singh RK, "HIF1alpha-regulated expression of the fatty acid binding protein family is important for hypoxic reactivation of Kaposi's Sarcoma-Associated Herpesvirus", J. Virol, 95, pp.e02063-20~ (2021)
  81. Choi UY, "Herpesvirus-induced spermidine synthesis and eIF5A hypusination for viral episomal maintenance", Cell Rep, 40, pp.111234~ (2022)

관련 논문AI추천

이 간행물의 다른 논문 (24건)