Department of Medical Microbiology, Qingdao University Medical College, Qingdao, China.
J Med Virol. 2010 May;82(5):829-36. doi: 10.1002/jmv.21714.
It has been generally believed that the Epstein-Barr virus (EBV)-encoded small RNA 1 and 2 (EBER1 and EBER2) genes are conserved as two families that correlated with type 1 (B95-8) and type 2 (AG876 or P3HR-1) EBV strains. EBER polymorphism and its association with EBV-associated disease have not received much attention. To explore the variations of EBER genes in different malignancies and healthy donors, the sequences of EBER genes were analyzed in 154 EBV-positive samples, including 47 nasopharyngeal carcinoma (NPC), 50 EBV-associated gastric carcinoma (EBVaGC) biopsies and 57 throat washing (TW) samples from healthy donors in northern China, where NPC is non-endemic. Three main distinct variants of EBER genes, designated as EB-6m, EB-8m, and EB-10m, were identified. EB-6m had a previously identified EBER sequence identical to P3HR-1 and was found in 33/47 (70.2%) NPC, 48/50 (96.0%) EBVaGC, and 54/57 (94.7%) TW isolates. EB-8m and EB-10m were new EBER variants with more mutations in EBER2 genes. They were found in 13/47 (27.7%) NPC cases, whereas in only 1/50 (2.0%) EBVaGC cases and not found in TW cases. The distributions were significantly different (P < 0.05). Other five isolates (one NPC, one EBVaGC and three TW cases) showed different sequences and could not be assigned to any of the three groups. Type 1 EBV strains showed heterogeneous in terms of EBER variants. These results suggest that EBER locus can be useful to identify different EBV isolates, and it would be interesting to evaluate the association of EBER polymorphisms with EBV-associated tumors.
人们普遍认为,Epstein-Barr 病毒(EBV)编码的小 RNA1 和 2(EBER1 和 EBER2)基因作为与 EBV 1 型(B95-8)和 2 型(AG876 或 P3HR-1)相关的两个家族而保守。EBER 多态性及其与 EBV 相关疾病的关联尚未受到太多关注。为了探讨 EBER 基因在不同恶性肿瘤和健康供体中的变化,分析了来自中国北方非鼻咽癌流行地区的 154 例 EBV 阳性样本中的 EBER 基因序列,包括 47 例鼻咽癌(NPC)、50 例 EBV 相关胃癌(EBVaGC)活检和 57 例健康供体咽拭子(TW)。鉴定出三种主要的 EBER 基因变体,分别命名为 EB-6m、EB-8m 和 EB-10m。EB-6m 具有与 P3HR-1 相同的先前鉴定的 EBER 序列,在 33/47(70.2%)例 NPC、48/50(96.0%)例 EBVaGC 和 54/57(94.7%)例 TW 分离株中发现。EB-8m 和 EB-10m 是 EBER2 基因中更多突变的新 EBER 变体。在 13/47(27.7%)例 NPC 病例中发现了它们,而在仅 1/50(2.0%)例 EBVaGC 病例中未发现,在 TW 病例中也未发现。分布有显著差异(P < 0.05)。其他 5 个分离株(1 个 NPC、1 个 EBVaGC 和 3 个 TW 病例)显示不同的序列,无法归入三组中的任何一组。1 型 EBV 株在 EBER 变体方面存在异质性。这些结果表明,EBER 基因座可用于识别不同的 EBV 分离株,评估 EBER 多态性与 EBV 相关肿瘤的关联将是有趣的。