Amino acid changes in functional domains of latent membrane protein 1 of Epstein-Barr virus in nasopharyngeal carcinoma of southern China and Taiwan: prevalence of an HLA A2-restricted 'epitope-loss variant'

Abstract

Full-length sequences of the Epstein-Barr virus (EBV) gene for latent membrane protein (LMP)-1 from 22 nasopharyngeal carcinoma (NPC) biopsy specimens and 18 non-neoplastic counterparts (NPI) were determined. Relative to the B95-8 strain, the amino acid sequences of the toxic-signal and transformation domains were changed variably in NPC and NPI specimens; in contrast, no change was observed in the NF-kappaB (nuclear factor kappaB) activation domain. HLA typing revealed that 47 % of NPC and 31 % of NPI specimens were HLA A2-positive. A major A2-restricted epitope within LMP-1 (residues 125-133) was analysed. At residue 126, a change of L-->F was detected in 91 % (20/22) of NPC and 67 % (12/18) of NPI specimens. In addition, a deletion at residue 126 was detected in one NPC sample from Taiwan. At residue 129, a change of M-->I was observed in all samples, regardless of whether they were NPC or NPI. The changes in this peptide between NPC and NPI specimens, including mutation and deletion, are statistically significant (P<0.05). A recent report indicated that this variant sequence is recognized poorly by epitope-specific T cells. Genotyping results indicated that 96 % of NPC and 67 % of NPI samples carried a type A virus. By scanning the entire sequence of LMP-1, eight distinct patterns were identified. Detailed examination of these patterns revealed that type A strains are more prevalent in NPC than in NPI specimens and are marked by the loss of an XhoI site, the presence of a 30 bp deletion and the presence of a mutated, A2-restricted, T cell target epitope sequence. These results suggest that an EBV strain carrying an HLA A2-restricted 'epitope-loss variant' of LMP-1 is prevalent in NPC in southern China and Taiwan.