Sample J, Brooks L, Sample C, Young L, Rowe M, Gregory C, Rickinson A, Kieff E
Department of Medicine, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6343-7. doi: 10.1073/pnas.88.14.6343.
Epstein-Barr virus (EBV) expresses six nuclear antigens (EBNAs) and three integral latent membrane proteins (LMPs) in latently infected growth-transformed B lymphoblastoid cell lines (LCLs). In contrast, EBV protein expression in Burkitt lymphoma tissue or in newly established Burkitt lymphoma cell lines is frequently restricted to the EBV genome maintenance protein, EBNA-1. EBNA-1 expression in the absence of other EBNAs and LMP-1 has been an enigma since, in LCLs, all EBNA mRNAs are processed from a single transcript. We now show that the basis for restricted EBV expression in Burkitt lymphoma cells is selective EBNA-1 mRNA transcription from a hitherto unrecognized promoter that is 50 kb closer to the EBNA-1-encoding exon than previously described EBNA-1 promoters. Infected cells with EBNA-1-restricted expression could preferentially persist in vivo in the face of EBV-immune T-cell responses, which are frequently directed against other EBNAs and are also dependent on LMP-1 expression.
在潜伏感染的生长转化B淋巴母细胞系（LCLs）中，爱泼斯坦-巴尔病毒（EBV）表达六种核抗原（EBNAs）和三种整合潜伏膜蛋白（LMPs）。相比之下，EBV蛋白在伯基特淋巴瘤组织或新建立的伯基特淋巴瘤细胞系中的表达通常局限于EBV基因组维持蛋白EBNA-1。由于在LCLs中所有EBNA mRNA均由单一转录本加工而来，因此在缺乏其他EBNAs和LMP-1的情况下EBNA-1的表达一直是个谜。我们现在表明，伯基特淋巴瘤细胞中EBV表达受限的基础是从一个迄今未被识别的启动子进行选择性EBNA-1 mRNA转录，该启动子比先前描述的EBNA-1启动子更靠近编码EBNA-1的外显子50 kb。面对通常针对其他EBNAs且也依赖LMP-1表达的EBV免疫T细胞反应，具有EBNA-1受限表达的感染细胞能够在体内优先存活。
