Nucleotide Sequences and Functions of the Epstein-Barr Virus Latent Membrane Protein 1 Genes Isolated from Salivary Gland Lymphoepithelial Carcinomas

Abstract

Epstein-Barr virus (EBV) infection is associated with salivary gland lymphoepithelial carcinoma (SLEC) and nasopharyngeal carcinoma (NPC). EBV is a ubiquitous herpes virus world wide, but EBV-associated SLEC and NPC are prevalent in restricted regions such as south areas of China, Southeastern Asia and Greenland (Eskimos). To examine whether particular EBV variants play roles in the development of SLEC and NPC, we isolated the complete EBV LMP1 genes from 12 paraffin-embedded biopsy samples of SLECs isolated from China, Taiwan and Russia, and compared these LMP1 genes with those of NPC (CAO) and the prototype B95-8 EBV. Nucleotide sequence analysis showed that SLECs LMP1 is more similar to that of CAO than that of prototype B95-8. The analysis also identified several conserved (67–100%) variations in SLEC-LMP1 and CAO-LMP1 distinct from B95-8-LMP1. These included 10-amino acid deletion, 5-amino acid deletion and 12-single amino acid variations. A SLEC-LMP1 gene with the aforementioned conserved variations inhibited the growth of an embryonic kidney cell line (293T), highly activated the NF-κB pathway, and these activities were equivalent to those of B95-8 and CAO. These findings suggest that the biological functions of SLEC-LMP 1 are similar to those of B95-8-LMP1 and CAO-LMP1, and that these amino acid variations including the well-known 10-aa deletion did not affect these two prominent activities. While the present results could not uncover functional differences between SLEC-LMP1 and B95-8-LMP1, the nucleotide sequences and the molecular clone of LMP1 directly isolated from SLEC patients will be a useful tool to identify the high-pathogenic EBV strain(s), associated with SLEC and NPC.