Function (s) of a novel Epstein-Barr virus latent gene, BARF0

eb病毒（EBV）与b细胞瘤、伯基特淋巴瘤、上皮性肿瘤、鼻咽癌和胃癌（GC）密切相关。在已知的潜伏性EBV基因中，只有有限数量的基因，如EBNA1、EBERs、LMP2A和最近发现的BARF0在EBV相关的人类恶性肿瘤中表达。然而，BARF0的功能尚不清楚，而EBNA1、EBERs和LMP2A的功能正在阐明。我们利用我们之前开发的有用的EBV体外上皮感染系统研究了BARF0在细胞恶性变化中的可能作用。将EBNA1、EBERs、BARF0、RK-BARF0和LMP2A的表达质粒分别导入正常培养的胃上皮细胞PGE-5 (j.v orrol；生物工程学报，73:1286- 92,1999)和表达每个基因的细胞克隆通过药物选择分离。在这些克隆中，表达BARF0和rk -BARF0的克隆在琼脂上的克隆性显著高于转染EBNA1-、EBER-、LMP2A-和neo^r基因的克隆，但低于感染ebv的克隆。另一项检查显示，在许多ebv感染的细胞系和来自GC和NPC组织的活检中，BARF0的表达水平始终高于RK-BARF0。综上所述，这些结果表明BARF0至少部分地对人胃上皮细胞具有致癌潜力。此外，由于在EBV感染的PGE-5细胞中所见的恶性表型不能仅由BARF0完全复制，因此可能存在其他未识别的EBV潜伏基因，负责上皮恶性改变。

Epstein-Barr virus (EBV) is closely associated with a B-cell tumor, Burkitt's lymphoma, and epithelial tumors, nasopharyngeal carcinoma and gastric carcinoma (GC). Among the known latent EBV genes, only a limited number of them, e.g. EBNA1, EBERs, LMP2A and recently identified BARF0, are expressed in the EBV-associated human malignancies. However, the function (s) of BARF0 is still unclear, whereas those of EBNA1, EBERs and LMP2A are being clarified. We investigated the possible role (s) of BARF0 in cellular malignant change by using the useful in vitro epithelial infection system by EBV, which we developed before.Expression plasmids for EBNA1, EBERs, BARF0, RK-BARF0 and LMP2A were introduced independently into a cultured normal gastric epithelial cell, PGE-5 (J.Virol., 73 : 1286-92, 1999), and its cell clones expressing each gene were isolated by drug selection. Among those clones, BARF0- and RK-BARF0-expressing clones showed a significantly higher clonability in agar than EBNA1-, EBER-, LMP2A- and neo^r gene-transfected ones, though lower than EBV-infected counterparts. Another examination showed that, in many EBV-infected cell lines and biopsies from GC and NPC tissues, BARF0 was consistently expressed at the much higher level than RK-BARF0. Taken together, these results suggest that BARF0 has oncogenic potential, at least partially, for human gastric epithelial cells. Additionally, since the malignant phenotype seen in EBV-infected PGE-5 cells was not fully reproduced by BARF0 alone, other unidentified EBV latent gene (s) responsible for epithelial malignant change may exist.