Sequence variations of Epstein–Barr virus LMP1 gene in gastric cancer and chronic gastritis isolates from Iranian patients

The aim of this study was to investigate sequence variations in the C-terminus of latent membrane protein 1 (LMP1) in Epstein-Barr virus (EBV) isolates from Iranian patients with chronic gastritis or gastric cancer (GC).

EBV is an important member of gammaherpesviruses that causes persisting latent human infection. LMP1 is the essential viral oncoprotein that is a key element for B cells immortalization. LMP1 contains of a small twenty-four amino acid cytoplasmic N-terminal region, six transmembrane segments and a two hundred amino acid cytoplasmic C-terminal domain. Most LMP1-mediated signal transduction events are moderated by some functional parts of cytoplasmic C-terminal domain. Sequence variations of LMP1 gene have been described in numerous EBV-isolates.

This study included 32 EBV positive biopsy tissues from patients with gastric cancer and patients with chronic gastritis. The C-terminal nucleotide sequences of LMP1 were amplified using nested-PCR and analyzed by DNA sequencing.

In the carboxyl-terminal site of patients was observed 4 to 8 copies of the 11 repeat elements (codon 254–302) and there was no relationship between the number of repeat sequences and disease status. The 30-bp deletion corresponding to codon 345–354 of the B95-8 strain was observed in 34% isolates and remaining samples were non-deleted. In group of gastric cancer, a high number of 33-bp repeats (>5 repeats) was observed in 30-bp-deletion (100%) than non-deleted (42%) isolates and the difference was also statistically significant. In addition, the analysis revealed that a gastritis isolate may be result of recombination between Alaskan and China1 strains.

Overall, our results showed no association between the C-terminal sequence variations of LMP1 and malignant or non-malignant isolate origin.