Functional Implications of Epstein-Barr Virus Lytic Genes in Carcinogenesis

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 Dec 11

PMID 36497262

Authors

Lee Fah Yap

Anna Kang Chee Wong

Ian C Paterson

Lawrence S Young

Affiliations

Soon will be listed here.

Abstract

Epstein-Barr virus (EBV) is associated with a diverse range of tumors of both lymphoid and epithelial origin. Similar to other herpesviruses, EBV displays a bipartite life cycle consisting of latent and lytic phases. Current dogma indicates that the latent genes are key drivers in the pathogenesis of EBV-associated cancers, while the lytic genes are primarily responsible for viral transmission. In recent years, evidence has emerged to show that the EBV lytic phase also plays an important role in EBV tumorigenesis, and the expression of EBV lytic genes is frequently detected in tumor tissues and cell lines. The advent of next generation sequencing has allowed the comprehensive profiling of EBV gene expression, and this has revealed the consistent expression of several lytic genes across various types of EBV-associated cancers. In this review, we provide an overview of the functional implications of EBV lytic gene expression to the oncogenic process and discuss possible avenues for future investigations.

Citing Articles

Anti-Epstein-Barr Virus Activities of Flavones and Flavonols with Effects on Virus-Related Cancers.

Hassan S Molecules. 2025; 30(5).

PMID: 40076282 PMC: 11902172. DOI: 10.3390/molecules30051058.

The 'Oma's of the Gammas-Cancerogenesis by γ-Herpesviruses.

Banerjee A, Dass D, Mukherjee S, Kaul M, Harshithkumar R, Bagchi P Viruses. 2025; 16(12.

PMID: 39772235 PMC: 11680331. DOI: 10.3390/v16121928.

The Functional Interaction Between Epstein-Barr Virus and MYC in the Pathogenesis of Burkitt Lymphoma.

Solares S, Leon J, Garcia-Gutierrez L Cancers (Basel). 2025; 16(24.

PMID: 39766110 PMC: 11674381. DOI: 10.3390/cancers16244212.

Immune Modulation by Epstein-Barr Virus Lytic Cycle: Relevance and Implication in Oncogenesis.

Todorovic N, Ambrosio M, Amedei A Pathogens. 2024; 13(10).

PMID: 39452747 PMC: 11510492. DOI: 10.3390/pathogens13100876.

A sarcomatoid malignancy originating in the right cervical lymph nodes with atypical pathological characteristics: a case report of an incidental finding.

Pan C, Jiang D, Huang J, Xu Z, Yang D, Xue F AME Case Rep. 2024; 8:71.

PMID: 39091555 PMC: 11292068. DOI: 10.21037/acr-23-147.

References

Murata T . Encyclopedia of EBV-Encoded Lytic Genes: An Update. Adv Exp Med Biol. 2018; 1045:395-412. DOI: 10.1007/978-981-10-7230-7_18. View

Uhlmann F . SMC complexes: from DNA to chromosomes. Nat Rev Mol Cell Biol. 2016; 17(7):399-412. DOI: 10.1038/nrm.2016.30. View

Shao Z, Borde C, Quignon F, Escargueil A, Marechal V . Epstein-Barr Virus BALF0 and BALF1 Modulate Autophagy. Viruses. 2019; 11(12). PMC: 6950364. DOI: 10.3390/v11121099. View

Wu C, Liu M, Chang Y, Fang C, Chou S, Liao H . Epstein-Barr virus DNase (BGLF5) induces genomic instability in human epithelial cells. Nucleic Acids Res. 2009; 38(6):1932-49. PMC: 2847232. DOI: 10.1093/nar/gkp1169. View

Lyngaa R, Norregaard K, Kristensen M, Kubale V, Rosenkilde M, Kledal T . Cell transformation mediated by the Epstein-Barr virus G protein-coupled receptor BILF1 is dependent on constitutive signaling. Oncogene. 2010; 29(31):4388-98. DOI: 10.1038/onc.2010.173. View

Abbott R, Quinn L, Leese A, Scholes H, Pachnio A, Rickinson A . CD8+ T cell responses to lytic EBV infection: late antigen specificities as subdominant components of the total response. J Immunol. 2013; 191(11):5398-409. PMC: 5580796. DOI: 10.4049/jimmunol.1301629. View

Bentz G, Liu R, Hahn A, Shackelford J, Pagano J . Epstein-Barr virus BRLF1 inhibits transcription of IRF3 and IRF7 and suppresses induction of interferon-beta. Virology. 2010; 402(1):121-8. PMC: 2871977. DOI: 10.1016/j.virol.2010.03.014. View

Rosemarie Q, Sugden B . Epstein-Barr Virus: How Its Lytic Phase Contributes to Oncogenesis. Microorganisms. 2020; 8(11). PMC: 7699388. DOI: 10.3390/microorganisms8111824. View

Babcock G, Decker L, Volk M, Thorley-Lawson D . EBV persistence in memory B cells in vivo. Immunity. 1998; 9(3):395-404. DOI: 10.1016/s1074-7613(00)80622-6. View

10.

Song L, Song M, Camargo M, Van Duine J, Williams S, Chung Y . Identification of anti-Epstein-Barr virus (EBV) antibody signature in EBV-associated gastric carcinoma. Gastric Cancer. 2021; 24(4):858-867. PMC: 8206016. DOI: 10.1007/s10120-021-01170-z. View

11.

Aubry V, Mure F, Mariame B, Deschamps T, Wyrwicz L, Manet E . Epstein-Barr virus late gene transcription depends on the assembly of a virus-specific preinitiation complex. J Virol. 2014; 88(21):12825-38. PMC: 4248913. DOI: 10.1128/JVI.02139-14. View

12.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

13.

Beisser P, Verzijl D, Gruijthuijsen Y, Beuken E, Smit M, Leurs R . The Epstein-Barr virus BILF1 gene encodes a G protein-coupled receptor that inhibits phosphorylation of RNA-dependent protein kinase. J Virol. 2004; 79(1):441-9. PMC: 538699. DOI: 10.1128/JVI.79.1.441-449.2005. View

14.

Xue W, Wang T, Huang J, Zhang J, He Y, Wu Z . A comprehensive analysis of genetic diversity of EBV reveals potential high-risk subtypes associated with nasopharyngeal carcinoma in China. Virus Evol. 2021; 7(1):veab010. PMC: 8458747. DOI: 10.1093/ve/veab010. View

15.

Nijmeijer S, Leurs R, Smit M, Vischer H . The Epstein-Barr virus-encoded G protein-coupled receptor BILF1 hetero-oligomerizes with human CXCR4, scavenges Gαi proteins, and constitutively impairs CXCR4 functioning. J Biol Chem. 2010; 285(38):29632-41. PMC: 2937994. DOI: 10.1074/jbc.M110.115618. View

16.

Song S, Jiang Z, Spezia-Lindner D, Liang T, Xu C, Wang H . BHRF1 Enhances EBV Mediated Nasopharyngeal Carcinoma Tumorigenesis through Modulating Mitophagy Associated with Mitochondrial Membrane Permeabilization Transition. Cells. 2020; 9(5). PMC: 7290790. DOI: 10.3390/cells9051158. View

17.

Nicholls J, Kremmer E, Meseda C, Mackett M, Hahn P, Gulley M . Comparative analysis of the expression of the Epstein-Barr virus (EBV) anti-apoptotic gene BHRF1 in nasopharyngeal carcinoma and EBV-related lymphoid diseases. J Med Virol. 2001; 65(1):105-13. View

18.

Zhang L, Wu H, Sun G, Xu X, Sun X, Cao L . Trichloromethane fraction of Incarvillea compacta induces lytic cytotoxicity and apoptosis in Epstein-Barr virus-positive gastric cancer AGS cells. BMC Complement Altern Med. 2016; 16:344. PMC: 5011811. DOI: 10.1186/s12906-016-1331-6. View

19.

Murono S, Inoue H, Tanabe T, Joab I, Yoshizaki T, Furukawa M . Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor production in nasopharyngeal carcinoma cells. Proc Natl Acad Sci U S A. 2001; 98(12):6905-10. PMC: 34451. DOI: 10.1073/pnas.121016998. View

20.

Zhu S, Sun P, Zhang Y, Yan L, Luo B . Expression of c-myc and PCNA in Epstein-Barr virus-associated gastric carcinoma. Exp Ther Med. 2013; 5(4):1030-1034. PMC: 3628757. DOI: 10.3892/etm.2013.972. View