Gutiérrez Marina I, Ibrahim Muna M, Dale Janet K, Greiner Timothy C, Straus Stephen E, Bhatia Kishor
King Fahad National Centre for Children's Cancer and Research (KFNCCC&R), King Faisal Specialist Hospital and Research Centre, Riyadh, 11211 Saudi Arabia.
J Natl Cancer Inst. 2002 Dec 4;94(23):1757-63. doi: 10.1093/jnci/94.23.1757.
Although the Epstein-Barr virus (EBV) is associated with malignant and nonmalignant diseases, its lytic replication is predominantly associated with nonmalignant diseases such as acute infectious mononucleosis (IM) or chronic active EBV infection. Lytic replication is also associated with type B EBV more than with type A EBV. Sustained lytic replication, however, is not compatible with tumor growth. We investigated whether control of an EBV lytic regulatory gene, BZLF1, differed in these diseases.
Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct DNA sequence analyses were used to characterize the promoter sequence of BZLF1 (Zp) in 52 tumors (34 non-Hodgkin's lymphomas, 13 post-transplant lymphoproliferative disease samples, and five nasopharyngeal carcinomas), and in peripheral blood lymphocytes from seven patients with chronic active EBV, six with IM, and 40 healthy, EBV-seropositive individuals. All sequences were compared with the prototype EBV strain B95.8 sequence. All statistical tests were two-sided.
Three polymorphic Zp sequences were detected. Among the malignant samples, sequence Zp-P, associated with 84% of type A EBV, was identical to that of EBV strain B95.8, whereas a second sequence (Zp-V3), associated exclusively with type B EBV (P<.001), contained three base substitutions. Among the nonmalignant samples, a distinct polymorphism, Zp-V4, containing the substitutions detected in Zp-V3 and an additional base change, was identified in all samples from chronic active EBV, IM, and healthy individuals, but in none of the malignant samples (P<.001). Zp-V4 was independent of the EBV type.
Polymorphisms in the regulatory sequences of BZLF1 are differentially distributed among malignant and nonmalignant cells and may identify EBV subtypes with various lytic activities, including those not associated with malignancies.
尽管爱泼斯坦-巴尔病毒（EBV）与恶性和非恶性疾病相关，但其裂解复制主要与非恶性疾病相关，如急性传染性单核细胞增多症（IM）或慢性活动性EBV感染。裂解复制与B型EBV的相关性也高于A型EBV。然而，持续的裂解复制与肿瘤生长不相容。我们研究了在这些疾病中EBV裂解调节基因BZLF1的调控是否存在差异。
采用聚合酶链反应-单链构象多态性（PCR-SSCP）和直接DNA序列分析来鉴定52个肿瘤（34例非霍奇金淋巴瘤、13例移植后淋巴细胞增殖性疾病样本和5例鼻咽癌）以及7例慢性活动性EBV患者、6例IM患者和40例健康EBV血清阳性个体外周血淋巴细胞中BZLF1（Zp）的启动子序列。所有序列均与EBV原型毒株B95.8序列进行比较。所有统计检验均为双侧检验。
检测到三种多态性Zp序列。在恶性样本中，与84%的A型EBV相关的序列Zp-P与EBV毒株B95.8的序列相同，而另一个仅与B型EBV相关的序列（Zp-V3）（P<0.001）含有三个碱基替换。在非恶性样本中，在慢性活动性EBV、IM和健康个体的所有样本中均鉴定出一种独特的多态性Zp-V4，其包含在Zp-V3中检测到的替换以及一个额外的碱基变化，但在恶性样本中均未检测到（P<0.001）。Zp-V4与EBV类型无关。
BZLF1调控序列中的多态性在恶性和非恶性细胞中分布不同，可能识别具有不同裂解活性的EBV亚型，包括那些与恶性肿瘤无关的亚型。
