Department of Medical Microbiology, Qingdao University Medical College, Qingdao, 266021, China.
J Med Virol. 2014 Oct;86(10):1788-95. doi: 10.1002/jmv.23911. Epub 2014 Feb 25.
The immediate-early (IE) genes, BZLF1 and BRLF1, play an important role in switching Epstein-Barr virus from the latent to the lytic state. The functions of the two IE genes and their respective proteins: ZEBRA and Rta have been well studied, but little is known about their DNA coding sequence variations and disease association. In order to investigate the sequence variation patterns and elucidate their association with lymphomas, BZLF1 and BRLF1 were analyzed in 26 and 33 lymphomas using PCR-direct sequencing method respectively. Three sequence variation types of BZLF1 gene were identified. The type BZLF1-A and BZLF1-B was detected in 34.6% (9/26) and 57.7% (15/26) of the tumor specimens, respectively. Among the three functional domains of ZEBRA, the transactivation domain had the most mutations. Three variation types were also identified in BRLF1 gene where type BR1-A and BR1-C were detected in 27.3% (9/33) and 69.7% (23/33) of specimens, respectively. Among the three functional domains of Rta, the dimerization domain was well conserved while multiple mutations were detected in both the DNA binding domain and the transactivation domain. The variation types BZLF1-B and BR1-C were more frequent in the lymphomas, compared with the throat washing samples from the healthy donors. These results suggest that the type BZLF1-B and BR1-C may be associated with the tumorigenesis of lymphoma.
立即早期（IE）基因 BZLF1 和 BRLF1 在 EBV 从潜伏状态向裂解状态转换中发挥重要作用。这两个 IE 基因及其各自的蛋白 ZEBRA 和 Rta 的功能已得到充分研究，但它们的 DNA 编码序列变异与疾病的关联知之甚少。为了研究序列变异模式并阐明其与淋巴瘤的关系，我们分别使用 PCR 直接测序法分析了 26 例和 33 例淋巴瘤中的 BZLF1 和 BRLF1。鉴定出 BZLF1 基因的三种序列变异类型。在 34.6%（26 例中的 9 例）和 57.7%（26 例中的 15 例）肿瘤标本中检测到 BZLF1-A 和 BZLF1-B 型。在 ZEBRA 的三个功能域中，转录激活域的突变最多。在 BRLF1 基因中也鉴定出三种变异类型，其中 BR1-A 和 BR1-C 型分别在 27.3%（33 例中的 9 例）和 69.7%（33 例中的 23 例）标本中检测到。在 Rta 的三个功能域中，二聚化结构域高度保守，而 DNA 结合域和转录激活域都检测到多个突变。与健康供体的咽喉冲洗样本相比，BZLF1-B 和 BR1-C 型在淋巴瘤中更为常见。这些结果表明，BZLF1-B 和 BR1-C 型可能与淋巴瘤的发生有关。
