Epstein-Barr virus-associated Burkitt lymphomagenesis selects for downregulation of the nuclear antigen EBNA2
Epstein-Barr virus-associated Burkitt lymphomagenesis selects for downregulation of the nuclear antigen EBNA2
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DOI：
10.1038/nm758
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发表时间：
2002-10-01
期刊：
影响因子：
82.9
通讯作者：
Rickinson, A
中科院分区：
文献类型：
--
作者：
Kelly, G;Bell, A;Rickinson, A
EB病毒(Epstein-Barr Virus，EBV)与地方性Burkitt淋巴瘤(BL)有关，但与染色体易位导致c-myc基因失控相比，EBV在淋巴肿大发生中的作用尚不清楚。病毒的生长转化(潜伏期III)程序的基因表达在肿瘤细胞中消失，只有一种病毒蛋白，EBV核抗原(EBNA)1，通过替代潜伏期I程序表达。目前尚不清楚BL是否起源于EBV自然接受潜伏期I感染的B细胞亚群，或者是否从EBV转化的潜伏期III祖细胞池中选择了抗原表达有限的克隆。在这里，我们确定了一组BL肿瘤，其中与潜伏期III相关的EBNA启动子WP是活跃的，并且大多数EBNAs都得到了表达，但其中一个基因缺失已经特异性地取消了EBNA2的表达。这意味着BL可以从潜伏期III的前体中选择，并且主要的选择压力是下调c-Myc拮抗剂EBNA2。
Epstein-Barr virus (EBV) is etiologically linked to endemic Burkitt lymphoma (BL), but its contribution to lymphomagenesis, versus that of the chromosomal translocation leading to c-myc gene deregulation, remains unclear. The virus's growth-transforming (Latency III) program of gene expression is extinguished in tumor cells, and only a single viral protein, the EBV nuclear antigen (EBNA) 1, is expressed via the alternative Latency I program. It is not known if BL arises from a B-cell subset in which EBV naturally adopts a Latency I infection or if a clone with limited antigen expression has been selected from an EBV-transformed Latency III progenitor pool. Here we identify a subset of BL tumors in which the Latency III-associated EBNA promoter Wp is active and most EBNAs are expressed, but where a gene deletion has specifically abrogated the expression of EBNA2. This implies that BL can be selected from a Latency III progenitor and that the principal selection pressure is for downregulation of the c-Myc antagonist EBNA2.