New Variations of Epstein-Barr Virus-Encoded Small RNA Genes in Nasopharyngeal Carcinomas, Gastric Carcinomas, and Healthy Donors in Northern China

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. J. Med. Virol. 82:829-836,2010. (C) 2010 Wiley-Liss, Inc.