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

新型 Epstein-Barr 病毒潜伏基因 BARF0 的功能

• 批准号: 11670286
• 负责人: IMAI Shosuke
• 金额: $ 2.3万
• 依托单位: Kochi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670286/
• 关键词: Epstein-Barr virus; BARF0 gene; Epithelial cells; Malignant change; 癌化

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.

EB病毒(EBV)与B细胞肿瘤、Burkitt淋巴瘤、上皮性肿瘤、鼻咽癌和胃癌密切相关。在已知的潜伏性EBV基因中，只有为数不多的EBNA1、EBERS、LMP2A和新近发现的BARF0基因在EBV相关的人类恶性肿瘤中表达。然而，BARF0的功能(S)仍然不清楚，而EBNA1、EBERS和LMP2A的功能正在被阐明。为探讨BARF0基因在细胞恶性转化中的作用，我们利用自行开发的EB病毒体外上皮细胞感染系统，将EBNA1、EBERS、BARF0、RK-BARF0和LMP2A5基因的表达载体分别导入正常胃上皮细胞PGE-5(J.Virol，73：1286-92,1999)，通过药物筛选获得表达每个基因的细胞克隆。在这些克隆中，表达BARF0和RK-BARF0的克隆在琼脂中的克隆能力显著高于EBNA1、EBER、LMP2A和neo^R基因转染者，但低于EBV感染的克隆。另一项检查表明，在许多EBV感染的细胞系以及来自GC和NPC组织的活检组织中，BARF0的表达水平始终高于RK-BARF0。综上所述，这些结果表明BARF0对人胃上皮细胞具有致癌潜力，至少部分是这样。此外，由于在EB病毒感染的PGE-5细胞中看到的恶性表型不能仅由BARF0完全复制，因此可能存在其他导致上皮恶变的未知EB病毒潜伏基因(S)。

项目成果

Imai S, et al.: "Basic biology of Epstein-Barr virus and recent progress."Crit.Rev.Oncol.Hematol.. (in press). (2001)

Imai S 等人：“Epstein-Barr 病毒的基础生物学和最新进展。”Crit.Rev.Oncol.Hematol..（正在出版）。

Imai S: "Cell-to-cell contact sa efficient mode of Epstein-Barr virus infection of diverse human epithelial cells."J.Virol. 72(5). 4371-4378 (1998)

Imai S：“细胞间接触是 Epstein-Barr 病毒感染多种人类上皮细胞的有效模式。”J.Virol。

Matsuzaki S, et al.: "Phylogeneticrelationship among T4-type bacteriophages in the Proteobacteria. In S.G.Pandalai (ed.)"Recent Research, Development in Virology. Transworld Research Network. Trivandrum India.. (in press). (2001)

Matsuzaki S 等人：“Proteobacteria 中 T4 型噬菌体之间的系统发育关系。S.G.Pandalai（编辑）”病毒学的最新研究和发展。

Tsutsumi H: "A boy with fatal infectious mononucleosis suspected as first Japanese case of X-linked lymphoproliferative syndrome."Scand.J.Infect.Dis.. 30(6). 610-612 (1998)

Tsutsumi H：“一名患有致命传染性单核细胞增多症的男孩被怀疑是日本首例 X 连锁淋巴增殖综合征病例。”Scand.J.Infect.Dis. 30(6)。

Oda T, et al.: "Epstein-Barr virus lacking glycoprotein gp85 cannot infect B cells and epithelial cells."Virology. 276. 52-58 (2000)

Oda T 等人：“缺乏糖蛋白 gp85 的 Epstein-Barr 病毒不能感染 B 细胞和上皮细胞。”病毒学。