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

EB病毒（EBV）与B细胞肿瘤、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，例如EBNA 1、EBER、LMP 2A和最近鉴定的BARF 0，在EBV相关的人类恶性肿瘤中表达。然而，BARF 0的功能仍不清楚，而EBNA 1、EBER和LMP 2A的功能正在阐明。将EBNA 1、EBER s、BARF 0、RK-BARF 0和LMP 2A的表达质粒分别导入培养的正常胃上皮细胞PGE-5（J.Virol.，73：1286-92，1999），并且通过药物选择分离表达每种基因的其细胞克隆。在这些克隆中，表达BARF 0和RK-BARF 0的克隆在琼脂中显示出比EBNA 1、EBER、LMP 2A和neo^r基因转染的克隆显著更高的克隆能力，尽管低于EBV感染的对应物。另一项研究表明，在许多EBV感染的细胞系和来自GC和NPC组织的活组织检查中，BARF 0的表达水平始终高于RK-BARF 0。总之，这些结果表明，BARF 0具有致癌潜力，至少部分，对人类胃上皮细胞。此外，由于在EBV感染的PGE-5细胞中观察到的恶性表型不能被单独的BARF 0完全复制，因此可能存在其他未鉴定的负责上皮恶性变化的EBV潜伏基因。

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.