The Therapeutic Potential of Targeting BARF1 in EBV-Associated Malignancies

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2020 Jul 26

PMID 32708965

Citations 14

Authors

Angela Kwok-Fung Lo

Christopher W Dawson

Hong Lok Lung

Ka-Leung Wong

Lawrence S Young

Affiliations

Soon will be listed here.

Abstract

Epstein-Barr virus (EBV) is closely linked to the development of a number of human cancers. EBV-associated malignancies are characterized by a restricted pattern of viral latent protein expression which is sufficient for the virus to both initiate and sustain cell growth and to protect virus-infected cells from immune attack. Expression of these EBV proteins in malignant cells provides an attractive target for therapeutic intervention. Among the viral proteins expressed in the EBV-associated epithelial malignancies, the protein encoded by the BamHI-A rightward frame 1 (BARF1) is of particular interest. BARF1 is a viral oncoprotein selectively expressed in latently infected epithelial cancers, nasopharyngeal carcinoma (NPC) and EBV-positive gastric cancer (EBV-GC). Here, we review the roles of BARF1 in oncogenesis and immunomodulation. We also discuss potential strategies for targeting the BARF1 protein as a novel therapy for EBV-driven epithelial cancers.

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References

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

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

Xue S, Labrecque L, Lu Q, Ong S, Lampert I, Kazembe P . Promiscuous expression of Epstein-Barr virus genes in Burkitt's lymphoma from the central African country Malawi. Int J Cancer. 2002; 99(5):635-43. DOI: 10.1002/ijc.10372. View

Elegheert J, Bracke N, Pouliot P, Gutsche I, Shkumatov A, Tarbouriech N . Allosteric competitive inactivation of hematopoietic CSF-1 signaling by the viral decoy receptor BARF1. Nat Struct Mol Biol. 2012; 19(9):938-47. DOI: 10.1038/nsmb.2367. View

Wang Y, Wang X, Sun Z, Luo B . Unique variations of Epstein-Barr virus-encoded BARF1 gene in nasopharyngeal carcinoma biopsies. Virus Res. 2012; 166(1-2):23-30. DOI: 10.1016/j.virusres.2012.02.022. View

Danve C, Decaussin G, Busson P, Ooka T . Growth transformation of primary epithelial cells with a NPC-derived Epstein-Barr virus strain. Virology. 2001; 288(2):223-35. DOI: 10.1006/viro.2001.1072. View

Young L, Yap L, Murray P . Epstein-Barr virus: more than 50 years old and still providing surprises. Nat Rev Cancer. 2016; 16(12):789-802. DOI: 10.1038/nrc.2016.92. View

Louis C, Straathof K, Bollard C, Ennamuri S, Gerken C, Lopez T . Adoptive transfer of EBV-specific T cells results in sustained clinical responses in patients with locoregional nasopharyngeal carcinoma. J Immunother. 2010; 33(9):983-90. PMC: 2964409. DOI: 10.1097/CJI.0b013e3181f3cbf4. View

Kalra M, Gerdemann U, Luu J, Ngo M, Leen A, Louis C . Epstein-Barr Virus (EBV)-derived BARF1 encodes CD4- and CD8-restricted epitopes as targets for T-cell immunotherapy. Cytotherapy. 2018; 21(2):212-223. PMC: 6435433. DOI: 10.1016/j.jcyt.2018.08.001. View

10.

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

11.

Knight J, Lan K, Bajaj B, Sharma N, Tsai D, Robertson E . A peptide-based inhibitor for prevention of B cell hyperproliferation induced by Epstein-Barr virus. Virology. 2006; 354(1):207-14. DOI: 10.1016/j.virol.2006.06.034. View

12.

Chang M, Kim D, Roh J, Middeldorp J, Kim Y, Kim S . Epstein-Barr virus-encoded BARF1 promotes proliferation of gastric carcinoma cells through regulation of NF-κB. J Virol. 2013; 87(19):10515-23. PMC: 3807382. DOI: 10.1128/JVI.00955-13. View

13.

Smith C, Tsang J, Beagley L, Chua D, Lee V, Li V . Effective treatment of metastatic forms of Epstein-Barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy. Cancer Res. 2012; 72(5):1116-25. DOI: 10.1158/0008-5472.CAN-11-3399. View

14.

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

15.

Hutajulu S, Hoebe E, Verkuijlen S, Fachiroh J, Hariwijanto B, Haryana S . Conserved mutation of Epstein-Barr virus-encoded BamHI-A Rightward Frame-1 (BARF1) gene in Indonesian nasopharyngeal carcinoma. Infect Agent Cancer. 2010; 5:16. PMC: 2949665. DOI: 10.1186/1750-9378-5-16. View

16.

Sall A, Caserta S, Jolicoeur P, Franqueville L, de Turenne-Tessier M, Ooka T . Mitogenic activity of Epstein-Barr virus-encoded BARF1 protein. Oncogene. 2004; 23(28):4938-44. DOI: 10.1038/sj.onc.1207607. View

17.

Jiang L, Lung H, Huang T, Lan R, Zha S, Chan L . Reactivation of Epstein-Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn-chelating function. Proc Natl Acad Sci U S A. 2019; 116(52):26614-26624. PMC: 6936348. DOI: 10.1073/pnas.1915372116. View

18.

de Turenne-Tessier M, Ooka T . Post-translational modifications of Epstein Barr virus BARF1 oncogene-encoded polypeptide. J Gen Virol. 2007; 88(Pt 10):2656-2661. DOI: 10.1099/vir.0.83058-0. View

19.

Hye-Ryong Shim A, Chang R, Chen X, Longnecker R, He X . Multipronged attenuation of macrophage-colony stimulating factor signaling by Epstein-Barr virus BARF1. Proc Natl Acad Sci U S A. 2012; 109(32):12962-7. PMC: 3420185. DOI: 10.1073/pnas.1205309109. View

20.

Kang M, Kieff E . Epstein-Barr virus latent genes. Exp Mol Med. 2015; 47:e131. PMC: 4314583. DOI: 10.1038/emm.2014.84. View