Abstract

The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is essential for Blymphocyte transformation, and activates NF-kB transcription factior in lymphocytes. LMP1 genes were isolated and sequenced from three type 1 isolates (SNU-321, SNU-538, and SNU-1103) and a type 2 isolate (SNU-20), all derived from Korean cancer pstients, to assess sequence variations in the LMP1 of Korean EBV isolates. Sequence analysis revealed that the SNU-1103 and SNU-20 LNP1 genes were nearly identical to that of the prototype B95-8 type 1 EBV strain, with 98% and 96% identities at the nucleotide and protein level, respectively. The SNU-321 and SNU-538 type 1 LMP1 genes both had a G to T substitution at nucleotide position 169,426, resulting in the loss of a XhoI site, and a carboxy-termina 30 base pair deletion (position 168,287-168,256), indicating they were variant LMP1 genes, as initially described in a Chinese nasopharyngeal carcinoma-derived EBV isolate (CAO). These two variant LMP1 genes shared more sequence variations than the SNU-20 and SNU-1103 IMP1 geres presumably associated with the LMP1 XhoI polymorphism, and showed 96% and 94% sequence identities, respectively, at the nucleotide and amino acid level to respective sequences of B95-8. There were consistent variations between all four isolates and B95-8, including 8-amino acid changes (B95-8 residues 85, 122, 129, 222, 309, 312, 334, 338, and 366) and a 5-amino acid deletion in the carboxy-terminal third 11-amino acid repeat. Transfection of each of these cloned LMP1 genes into Jurkat cells resulted in tenfold stimulation of NF-kB activity, confirming functionality of LMP1 proteins expressed from these genes. Taken together, these results indicate that there is a high degree of overall conservation in sequences of LMP1 between different EBV isolates, yet the distinct sequence variation patterns are consistent with the notion that there are at least two distinct LMP1 variants.

• Keywords: Epstein-Barr virus; latent membrance protein 1; sequence variation; a 30-bp deleted LMP1 variant