ISSN: 2008-2258
Vol 15, No 3 (2022): Summer
Sequence variations of Epstein–Barr virus LMP1 gene in gastric cancer and chronic gastritis isolates from Iranian patients EBV LMP1 variations in GC and chronic gastritis patients
Gastroenterology and Hepatology from Bed to Bench,
,
https://doi.org/10.22037/ghfbb.v15i3.2578
Abstract
Aim: The current study aimed 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).
Background: LMP1 is the essential viral oncoprotein that is a key element in the immortalization of B cells. It contains 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 the cytoplasmic C-terminal domain.
Methods: Thirty-two EBV positive biopsy tissues were obtained 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.
Results Four to eight copies of the 11 repeat elements (codon 254–302) were observed in the carboxyl-terminal site of patients, but no relationship was found 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% of isolates, and the remaining samples were non-deleted. In the gastric cancer group, a higher number of 33-bp repeats (≥5 repeats) was observed in 30-bp-deletion (100%) than in non-deleted (42%) isolates, and the difference was statistically significant. Analysis revealed that a gastritis isolate may be the result of recombination between Alaskan and China1 strains.
Conclusion: Overall, the current results showed no association between C-terminal sequence variations of LMP1 and malignant or non-malignant isolate origin.
- EBV
- latent membrane protein 1
- sequence variations
- repeat elements
How to Cite
References
Chen M-R. Epstein–Barr virus, the immune system, and associated diseases. Front Microbiol 2011;2:5.
Gequelin LCF, Riediger IN, Nakatani SM, Biondo AW, Bonfim CM. Epstein-Barr virus: General factors, virus-related diseases and measurement of viral load after transplant. Rev Bras Hematol Hemoter 2011;33:383-8.
Neparidze N, Lacy J. Malignancies associated with epstein-barr virus: pathobiology, clinical features, and evolving treatments. Clin Adv Hematol Oncol 2014;12:358-71.
Jia X, Guo T, Li Z, Zhang M, Feng Y, Dong B, et al. Clinicopathological and immunomicroenvironment characteristics of Epstein–Barr virus-associated gastric cancer in a chinese population. Front Oncol 2021;10:586752.
Ribeiro J, Oliveira C, Malta M, Sousa H. Epstein–Barr virus gene expression and latency pattern in gastric carcinomas: a systematic review. Future Oncol 2017;13:567-79.
Banko A, Miljanovic D, Lazarevic I, Cirkovic A. A systematic review of Epstein–Barr virus latent membrane protein 1 (LMP1) gene variants in nasopharyngeal carcinoma. Pathogens 2021;10:1057.
Edwards RH, Seillier-Moiseiwitsch F, Raab-Traub N. Signature amino acid changes in latent membrane protein 1 distinguish Epstein–Barr virus strains. Virology 1999;261:79-95.
Wang H-Y, Sun L, Li P, Liu W, Zhang Z-G, Luo B. Sequence variations of Epstein-Barr virus-encoded small noncoding rna and latent membrane protein 1 in hematologic tumors in northern china. Intervirology 2021;64:69-80.
Ranger-Rogez S. EBV genome mutations and malignant proliferations. In: Drouet, E. ed. Epstein-Barr Virus - New Trends [Internet]. London: IntechOpen; 2020. Available from: https://www.intechopen.com/chapters/73024.
Knecht H, Bachmann E, Brousset P, Sandvej K, Nadal D, Bachmann F, et al. Deletions within the LMP1 oncogene of Epstein-Barr virus are clustered in Hodgkin's disease and identical to those observed in nasopharyngeal carcinoma. Blood 1993;82:2937-42.
Brinkmann MM, Schulz TF. Regulation of intracellular signalling by the terminal membrane proteins of members of the Gammaherpesvirinae. J Gen Virol 2006;87:1047-74.
Neves M, Marinho‐Dias J, Ribeiro J, Sousa H. Epstein–Barr virus strains and variations: Geographic or disease‐specific variants? J Med Virol 2017;89:373-87.
Mainou BA, Raab-Traub N. LMP1 strain variants: Biological and molecular properties. J Virol 2006;80:6458-68.
Li S-N, Chang Y-S, Liu S-T. Effect of a 10-amino acid deletion on the oncogenic activity of latent membrane protein 1 of Epstein-Barr virus. Oncogene 1996;12:2129-35.
BenAyed-Guerfali D, Ayadi W, Miladi-Abdennadher I, Khabir A, Sellami-Boudawara T, Gargouri A, et al. Characteristics of epstein barr virus variants associated with gastric carcinoma in Southern Tunisia. Virol J 2011;8:1-9.
Chen JN, Ding YG, Feng ZY, Li HG, He D, Du H, et al. Association of distinctive Epstein–Barr virus variants with gastric carcinoma in Guangzhou, Southern China. J Med Virol 2010;82:658-67.
Chen J-n, Jiang Y, Li H-g, Ding Y-g, Fan X-j, Xiao L, et al. Epstein-Barr virus genome polymorphisms of Epstein-Barr virus-associated gastric carcinoma in gastric remnant carcinoma in Guangzhou, Southern China, An endemic area of nasopharyngeal carcinoma. Virus Res 2011;160:191-9.
Cheng N, Hui D-y, Liu Y, Zhang N-n, Jiang Y, Han J, et al. Is gastric lymphoepithelioma-like carcinoma a special subtype of EBV-associated gastric carcinoma? New insight based on clinicopathological features and EBV genome polymorphisms. Gastric Cancer 2015;18:246-55.
Ai J, Xie Z, Liu C, Huang Z, Xu J. Analysis of EBNA-1 and LMP-1 variants in diseases associated with EBV infection in Chinese children. Virol J 2012;9:1-8.
Fukayama M, Ushiku T. Epstein-Barr virus-associated gastric carcinoma. Pathol Res Pract 2011;207:529-37.
See HS, Yap YY, Yip WK, Seow HF. Epstein-Barr virus latent membrane protein-1 (LMP-1) 30-bp deletion and Xho I-loss is associated with type III nasopharyngeal carcinoma in Malaysia. World J Surg Oncol 2008;6:1-10.
Huen D, Henderson S, Croom-Carter D, Rowe M. The Epstein-Barr virus latent membrane protein-1 (LMP1) mediates activation of NF-kappa B and cell surface phenotype via two effector regions in its carboxy-terminal cytoplasmic domain. Oncogene 1995;10:549-60.
Moorthy RK, Thorley-Lawson DA. Biochemical, genetic, and functional analyses of the phosphorylation sites on the Epstein-Barr virus-encoded oncogenic latent membrane protein LMP-1. J Virol 1993;67:2637-45.
Kanai K, Satoh Y, Saiki Y, Ohtani H, Sairenji T. Difference of Epstein–Barr virus isolates from Japanese patients and African Burkitt’s lymphoma cell lines based on the sequence of latent membrane protein 1. Virus Genes 2007;34:55-61.
Jovanovic T. Analysis of the variability of epstein-barr virus genes in infectious mononucleosis: Investigation of the potential correlation with biochemical parameters of hepatic involvement. J Med Biochem 2016;35:337-46.
Miller WE, Edwards RH, Walling DM, Raab-Traub N. Sequence variation in the Epstein–Barr virus latent membrane protein 1. J Gen Virol 1994;75:2729-40.
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