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

BamHI-A rightward frame 1, an Epstein-Barr virus-encoded oncogene and immune modulator.
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DOI:
10.1002/rmv.1758
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发表时间:
2013-11
影响因子:
11.1
通讯作者:
Middeldorp, Jaap M.
Middeldorp, Jaap M.
中科院分区:
医学2区
文献类型:
--
作者:
Hoebe, Eveline K.;Le Large, Tessa Y. S.;Greijer, Astrid E.;Middeldorp, Jaap M.

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EB病毒(EBV)引起淋巴和上皮起源的几种良性和恶性疾病。EBV相关肿瘤显示出不同的病毒潜伏基因表达模式,其中BamHI-A转录框1(BARF 1)在癌中选择性表达,受包括Δ Np 63 α在内的细胞分化因子调节。BARF 1作为一种病毒致癌基因发挥作用,通过作为促有丝分裂生长因子、诱导细胞周期蛋白-D表达和上调抗凋亡Bcl-2、刺激宿主细胞生长和存活,使不同来源的上皮细胞永生化和转化。此外,分泌的六聚体BARF 1具有免疫逃避特性,在功能上破坏巨噬细胞集落刺激因子,如最近的功能和结构数据所支持的。因此,BARF 1作为一种细胞内分泌蛋白,不仅具有多种致病功能,而且可以作为免疫应答的靶点。破译BARF 1在EBV生物学中的作用将有助于为EBV驱动的癌症提供新的诊断和治疗选择。在此,我们讨论了最近的见解,调节BARF 1的表达和方面的结构功能有关的致癌和免疫抑制特性。© 2013作者。出版社:John Wiley & Sons,Ltd.
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.
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