Hu L F, Chen F, Altiok E, Winberg G, Klein G, Ernberg I
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
Gan To Kagaku Ryoho. 2000 May;27 Suppl 2:248-60.
Three types of virus-host cell interactions have been described in cells latently infected with EBV: EBNA 1 expression in type I Burkitt's lymphoma cell lines (BL), EBNA 1, LMP1 and 2 expression in most nasopharyngeal carcinomas (NPC) and EBNA 1-6 with LMP 1 and 2 expression in group III BL-lines as well as lymphoblastoid cell lines (LCL). Two group I BL lines that express only EBNA 1 were found to initiate their EBNA 1 mRNA transcription from a promoter in the Bam HI Q-fragment. They use a sequence at +210 bp relative to the Fp transcription initiation site in group I BL cell lines. The Fp promoter-region seems to be activated in the lytic cycle. LCLs initiate their transcription from one of several upstream sites, usually the Cp promoter or, less frequently, one of several Wp-promoters. Using RNA-reverse transcription polymerase chain reaction (RT-PCR), we have now shown that EBV carrying cells that do not express EBNA 2-6 always splice their EBNA mRNA at the Q-exon, while EBNA 2-6 positive cells use either the Cp or one of the Wp promotors. When EBNA 2-6 are downregulated by somatic cell hybridisation between EBNA 1-6 positive B-cell lines and non B-cells of hematopoetic, epithelial or fibroblastic origin that express the phenotype of the non-B cell parent, the parental usage of Cp/Wp is switched off, and the Q-exon is activated. NPC cells show the same pattern of promoter usage as the hybrids with non-B phenotype. Group III BL cells use both promoter regions. Thus, the virus can use two alternative programs, depending on the cell phenotype. The "EBNA-1 only" program is activated from the Q-promoter. In cells with an immunoblastic (LCL or BL group III) phenotype, the upstream Cp/Wp promoters generate a 100 kb. long pre-mRNA, from which all the EBNAs are spliced. As a rule, only one of the two programs is used for each phenotype, except for the BL group III cells that began as group I but subsequently developed into a more LCL-like cell. Such cells used both promoter regions, with or without activation of the lytic cycle.
在潜伏感染EBV的细胞中，已描述了三种病毒-宿主细胞相互作用类型：I型伯基特淋巴瘤细胞系（BL）中EBNA 1的表达；大多数鼻咽癌（NPC）中EBNA 1、LMP1和LMP2的表达；III组BL细胞系以及淋巴母细胞系（LCL）中EBNA 1-6与LMP 1和LMP2的表达。发现仅表达EBNA 1的两个I组BL细胞系从Bam HI Q片段中的一个启动子起始其EBNA 1 mRNA转录。它们在I组BL细胞系中相对于Fp转录起始位点的+210 bp处使用一个序列。Fp启动子区域似乎在裂解周期中被激活。LCL从几个上游位点之一起始转录，通常是Cp启动子，或较少见的是几个Wp启动子之一。使用RNA逆转录聚合酶链反应（RT-PCR），我们现已表明，不表达EBNA 2-6的携带EBV的细胞总是在Q外显子处剪接其EBNA mRNA，而EBNA 2-6阳性细胞则使用Cp或Wp启动子之一。当通过EBNA 1-6阳性B细胞系与表达非B细胞亲本表型的造血、上皮或成纤维细胞来源的非B细胞之间的体细胞杂交使EBNA 2-6下调时，Cp/Wp的亲本使用方式被关闭，且Q外显子被激活。NPC细胞显示出与具有非B表型的杂交细胞相同的启动子使用模式。III组BL细胞使用两个启动子区域。因此，病毒可根据细胞表型使用两种替代程序。“仅EBNA-1”程序从Q启动子被激活。在具有免疫母细胞（LCL或III组BL）表型的细胞中，上游Cp/Wp启动子产生一个100 kb长的前体mRNA，所有EBNA均从此前体mRNA中剪接而来。通常，每种表型仅使用两种程序中的一种，但起始为I组但随后发展成更类似LCL样细胞的III组BL细胞除外。此类细胞使用两个启动子区域，无论裂解周期是否被激活。
