BamHI-A rightward frame 1, an Epstein-Barr virus-encoded oncogene and immune modulator

• Published in: Reviews in medical virology Vol. 23; no. 6; pp. 367 - 383
• Main Authors: Hoebe, Eveline K., Le Large, Tessa Y. S., Greijer, Astrid E., Middeldorp, Jaap M.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.11.2013; Wiley Periodicals Inc; BlackWell Publishing Ltd
• Subjects: Cell Transformation, Viral; Epstein-Barr virus; Herpesvirus 4, Human - immunology; Herpesvirus 4, Human - physiology; Host-Pathogen Interactions; Humans; Immune Evasion; Oncogene Proteins, Viral - immunology; Oncogene Proteins, Viral - metabolism; Reviews; Viral Proteins - immunology; Viral Proteins - metabolism
• ISSN: 1052-9276; 1099-1654
• DOI: 10.1002/rmv.1758

SUMMARY 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. © 2013 The Authors. Reviews in Medical Virology published by John Wiley & Sons, Ltd.