Epstein-Barr virus nuclear antigen 2 specifically induces expression of the B-cell activation antigen CD23.
Epstein-Barr virus nuclear antigen 2 specifically induces expression of the B-cell activation antigen CD23.
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Epstein-Barr 病毒核抗原 2 特异性诱导 B 细胞激活抗原 CD23 的表达。
DOI：
10.1073/pnas.84.10.3452
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发表时间：
1987
影响因子：
11.1
通讯作者：
Kieff,E
中科院分区：
文献类型：
--
作者：
Wang,F;Gregory,CD;Rowe,M;Rickinson,AB;Wang,D;Birkenbach,M;Kikutani,H;Kishimoto,T;Kieff,E
EB病毒（EBV）感染EBV阴性伯基特淋巴瘤（BL）细胞诱导的一些变化类似于在已被EBV生长转化的正常B淋巴细胞中观察到的变化。通过使用重组逆转录病毒介导的转移，将在EBV生长转化和潜伏感染的淋巴母细胞中正常表达的每种病毒基因引入EBV阴性BL细胞系中，来评价单个EBV基因在该过程中的作用。衍生稳定表达EBV核抗原1（EBNA-1）、EBNA-2、EBNA-3、EBNA-前导蛋白或EBV潜伏膜蛋白（LMP）的细胞克隆。将这些与用逆转录病毒载体感染的对照克隆进行比较。转化为EBNA-2表达的所有10个克隆与对照克隆或表达其他EBV蛋白的克隆的不同之处在于以紧密的团块生长和B细胞活化的一种特定表面标志物CD 23的表达显著增加。其他活化抗原不受EBNA-2表达的影响，如在亲本BL细胞系上已经表达的标志物，包括BL标志物（cALLA和BLA）、增殖标志物（转铁蛋白受体和BK 19.9）和细胞粘附相关分子（LFA-1和LFA-3）。从单克隆抗CD 23抗体与细胞表面的结合、用单克隆抗体对45-kDa和90-kDa CD 23蛋白的免疫沉淀以及用标记的CD 23 DNA探测的RNA印迹中，可以明显看出表达EBNA-2的细胞中CD 23表达的增加。结果表明EBNA-2是CD 23的特异性直接或间接反式激活因子。这建立了EBV基因和细胞基因表达之间的联系。由于CD 23与B细胞生长信号的转导有关，EBNA-2对其的特异性诱导在EBV诱导B淋巴细胞转化中可能是重要的。
Epstein-Barr virus (EBV) infection of EBV-negative Burkitt lymphoma (BL) cells induces some changes similar to those seen in normal B lymphocytes that have been growth transformed by EBV. The role of individual EBV genes in this process was evaluated by introducing each of the viral genes that are normally expressed in EBV growth-transformed and latently infected lymphoblasts into an EBV-negative BL cell line, using recombinant retrovirus-mediated transfer. Clones of cells were derived that stably express the EBV nuclear antigen 1 (EBNA-1), EBNA-2, EBNA-3, EBNA-leader protein, or EBV latent membrane protein (LMP). These were compared with control clones infected with the retrovirus vector. All 10 clones converted to EBNA-2 expression differed from control clones or clones expressing other EBV proteins by growth in tight clumps and by markedly increased expression of one particular surface marker of B-cell activation, CD23. Other activation antigens were unaffected by EBNA-2 expression, as were markers already expressed on the parent BL cell line, including BL markers (cALLA and BLA), proliferation markers (transferrin receptor and BK19.9), and cell adhesion-related molecules (LFA-1 and LFA-3). Increased CD23 expression in cells expressing EBNA-2 was apparent from monoclonal anti-CD23 antibody binding to the cell surface, from immunoprecipitation of the 45-kDa and 90-kDa CD23 proteins with monoclonal antibody, and from RNA blots probed with labeled CD23 DNA. The results indicate that EBNA-2 is a specific direct or indirect trans-activator of CD23. This establishes a link between an EBV gene and cell gene expression. Since CD23 has been implicated in the transduction of B-cell growth signals, its specific induction by EBNA-2 could be important in EBV induction of B-lymphocyte transformation.