BamHI-A Rightward Frame 1, an Epstein-Barr Virus-encoded Oncogene and Immune Modulator

Overview

Journal Rev Med Virol

Publisher Wiley

Specialty Microbiology

Date 2013 Sep 3

PMID 23996634

Citations 31

Authors

Eveline K Hoebe

Tessa Y S Le Large

Astrid E Greijer

Jaap M Middeldorp

Affiliations

Soon will be listed here.

Abstract

Epstein-Barr virus (EBV) causes several benign and malignant disorders of lymphoid and epithelial origin. EBV-related tumors display distinct patterns of viral latent gene expression, of which the BamHI-A rightward frame 1 (BARF1) is selectively expressed in carcinomas, regulated by cellular differentiation factors including ΔNp63α. BARF1 functions as a viral oncogene, immortalizing and transforming epithelial cells of different origin by acting as a mitogenic growth factor, inducing cyclin-D expression, and up-regulating antiapoptotic Bcl-2, stimulating host cell growth and survival. In addition, secreted hexameric BARF1 has immune evasive properties, functionally corrupting macrophage colony stimulating factor, as supported by recent functional and structural data. Therefore, BARF1, an intracellular and secreted protein, not only has multiple pathogenic functions but also can function as a target for immune responses. Deciphering the role of BARF1 in EBV biology will contribute to novel diagnostic and treatment options for EBV-driven carcinomas. Herein, we discuss recent insights on the regulation of BARF1 expression and aspects of structure-function relating to its oncogenic and immune suppressive properties.

Citing Articles

Epstein-Barr Virus BARF1 Is Expressed in Lung Cancer and Is Associated with Cancer Progression.

Osorio J, Armijo A, Carvajal F, Corvalan A, Castillo A, Fuentes-Panana E Cells. 2024; 13(18.

PMID: 39329759 PMC: 11430695. DOI: 10.3390/cells13181578.

VLDL and LDL Subfractions Enhance the Risk Stratification of Individuals Who Underwent Epstein-Barr Virus-Based Screening for Nasopharyngeal Carcinoma: A Multicenter Cohort Study.

Zhou Z, Tang T, Li N, Zheng Q, Xiao T, Tian Y Adv Sci (Weinh). 2024; 11(22):e2308765.

PMID: 38520712 PMC: 11165512. DOI: 10.1002/advs.202308765.

Can the Epstein-Barr Virus Play a Role in the Development of Prostate Cancer?.

Kis J, Goralczyk M, Sikora D, Stepien E, Drop B, Polz-Dacewicz M Cancers (Basel). 2024; 16(2).

PMID: 38254816 PMC: 10814141. DOI: 10.3390/cancers16020328.

Contribution of Epstein-Barr Virus Lytic Proteins to Cancer Hallmarks and Implications from Other Oncoviruses.

Dorothea M, Xie J, Yiu S, Chiang A Cancers (Basel). 2023; 15(7).

PMID: 37046781 PMC: 10093119. DOI: 10.3390/cancers15072120.

A Standardized Pathology Report for Gastric Cancer: 2nd Edition.

Park Y, Kook M, Kim B, Lee H, Kang D, Gu M J Gastric Cancer. 2023; 23(1):107-145.

PMID: 36750994 PMC: 9911618. DOI: 10.5230/jgc.2023.23.e7.

References

Hatfull G, Bankier A, Barrell B, Farrell P . Sequence analysis of Raji Epstein-Barr virus DNA. Virology. 1988; 164(2):334-40. DOI: 10.1016/0042-6822(88)90546-6. View

Sugawara Y, Mizugaki Y, Uchida T, Torii T, Imai S, Makuuchi M . Detection of Epstein-Barr virus (EBV) in hepatocellular carcinoma tissue: a novel EBV latency characterized by the absence of EBV-encoded small RNA expression. Virology. 1999; 256(2):196-202. DOI: 10.1006/viro.1999.9619. View

Xue S, Lampert I, Haldane J, Bridger J, Griffin B . Epstein-Barr virus gene expression in human breast cancer: protagonist or passenger?. Br J Cancer. 2003; 89(1):113-9. PMC: 2394222. DOI: 10.1038/sj.bjc.6601027. View

Sheng W, Decaussin G, Ligout A, Takada K, Ooka T . Malignant transformation of Epstein-Barr virus-negative Akata cells by introduction of the BARF1 gene carried by Epstein-Barr virus. J Virol. 2003; 77(6):3859-65. PMC: 149494. DOI: 10.1128/jvi.77.6.3859-3865.2003. View

Lo K, Huang D . Genetic and epigenetic changes in nasopharyngeal carcinoma. Semin Cancer Biol. 2002; 12(6):451-62. DOI: 10.1016/s1044579x02000883. View

Hoebe E, Hutajulu S, van Beek J, Stevens S, Paramita D, Greijer A . Purified hexameric Epstein-Barr virus-encoded BARF1 protein for measuring anti-BARF1 antibody responses in nasopharyngeal carcinoma patients. Clin Vaccine Immunol. 2010; 18(2):298-304. PMC: 3067345. DOI: 10.1128/CVI.00193-10. View

Fachiroh J, Paramita D, Hariwiyanto B, Harijadi A, Dahlia H, Indrasari S . Single-assay combination of Epstein-Barr Virus (EBV) EBNA1- and viral capsid antigen-p18-derived synthetic peptides for measuring anti-EBV immunoglobulin G (IgG) and IgA antibody levels in sera from nasopharyngeal carcinoma patients: options for.... J Clin Microbiol. 2006; 44(4):1459-67. PMC: 1448657. DOI: 10.1128/JCM.44.4.1459-1467.2006. View

Fahraeus R, Fu H, Ernberg I, Finke J, Rowe M, Klein G . Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma. Int J Cancer. 1988; 42(3):329-38. DOI: 10.1002/ijc.2910420305. View

Fukushima N, Satoh T, Sueoka N, Sato A, Ide M, Hisatomi T . Clinico-pathological characteristics of p63 expression in B-cell lymphoma. Cancer Sci. 2006; 97(10):1050-5. PMC: 11159472. DOI: 10.1111/j.1349-7006.2006.00284.x. View

10.

Rezk S, Weiss L . Epstein-Barr virus-associated lymphoproliferative disorders. Hum Pathol. 2007; 38(9):1293-304. DOI: 10.1016/j.humpath.2007.05.020. View

11.

Zhang Y, Ohyashiki J, Takaku T, Shimizu N, Ohyashiki K . Transcriptional profiling of Epstein-Barr virus (EBV) genes and host cellular genes in nasal NK/T-cell lymphoma and chronic active EBV infection. Br J Cancer. 2006; 94(4):599-608. PMC: 2361178. DOI: 10.1038/sj.bjc.6602968. View

12.

van Beek J, Brink A, Vervoort M, van Zijp M, Meijer C, van den Brule A . In vivo transcription of the Epstein-Barr virus (EBV) BamHI-A region without associated in vivo BARF0 protein expression in multiple EBV-associated disorders. J Gen Virol. 2003; 84(Pt 10):2647-2659. DOI: 10.1099/vir.0.19196-0. View

13.

Smith P, de Jesus O, Turner D, Hollyoake M, Karstegl C, Griffin B . Structure and coding content of CST (BART) family RNAs of Epstein-Barr virus. J Virol. 2000; 74(7):3082-92. PMC: 111807. DOI: 10.1128/jvi.74.7.3082-3092.2000. View

14.

Griffin B, Karran L . Immortalization of monkey epithelial cells by specific fragments of Epstein-Barr virus DNA. Nature. 1984; 309(5963):78-82. DOI: 10.1038/309078a0. View

15.

Karran L, Teo C, King D, Hitt M, Gao Y, Wedderburn N . Establishment of immortalized primate epithelial cells with sub-genomic EBV DNA. Int J Cancer. 1990; 45(4):763-72. DOI: 10.1002/ijc.2910450432. View

16.

Brink A, Vervoort M, Middeldorp J, Meijer C, van den Brule A . Nucleic acid sequence-based amplification, a new method for analysis of spliced and unspliced Epstein-Barr virus latent transcripts, and its comparison with reverse transcriptase PCR. J Clin Microbiol. 1998; 36(11):3164-9. PMC: 105294. DOI: 10.1128/JCM.36.11.3164-3169.1998. View

17.

Tugizov S, Herrera R, Veluppillai P, Greenspan J, Greenspan D, Palefsky J . Epstein-Barr virus (EBV)-infected monocytes facilitate dissemination of EBV within the oral mucosal epithelium. J Virol. 2007; 81(11):5484-96. PMC: 1900306. DOI: 10.1128/JVI.00171-07. View

18.

van Beek J, Zur Hausen A, Kranenbarg E, van de Velde C, Middeldorp J, van den Brule A . EBV-positive gastric adenocarcinomas: a distinct clinicopathologic entity with a low frequency of lymph node involvement. J Clin Oncol. 2004; 22(4):664-70. DOI: 10.1200/JCO.2004.08.061. View

19.

Seto E, Ooka T, Middeldorp J, Takada K . Reconstitution of nasopharyngeal carcinoma-type EBV infection induces tumorigenicity. Cancer Res. 2008; 68(4):1030-6. DOI: 10.1158/0008-5472.CAN-07-5252. View

20.

Meij P, Leen A, Rickinson A, Verkoeijen S, Vervoort M, Bloemena E . Identification and prevalence of CD8(+) T-cell responses directed against Epstein-Barr virus-encoded latent membrane protein 1 and latent membrane protein 2. Int J Cancer. 2002; 99(1):93-9. DOI: 10.1002/ijc.10309. View