Molecular characterization of Epstein-Barr virus variants detected in the oral cavity of adolescents in Cali, Colombia
Abstract
Introduction: The Epstein-Barr virus (EBV) is an ubiquitous and oncogenic virus associated with the development of diseases such as infectious mononucleosis, Burkitt’s lymphoma, nasopharyngeal carcinoma, and other neoplasms. Currently, two types are recognized: EBV-1 and EBV-2, which have genetic differences with their EBNA nuclear antigens. Likewise, due to the high degree of heterogeneity and variability found in the LMP1 protein of the virus, variants associated with pathogenesis or specific geographic regions have been described.
Objective: To identify and characterize molecularly EBV variants detected in the oral cavity of 84 adolescents in Cali, Colombia.
Materials and methods: Conventional PCR amplification, purification, and sequencing of the gen EBNA3C were carried out to typify the virus and the C-ter domain of the LMP1 protein to identify variants. We also conducted a phylogenetic and nucleotide variant analysis of the obtained sequences versus pathogenic or geographic variants reported in GenBank-NCBI.
Results: The predominant viral subtype was EBV-1 (79%); 72.6% was grouped with the pathogenic variant Raji, derived from B lymphocytes of a patient with Burkitt›s lymphoma, 13.7% was related to a variant of Mediterranean origin, and 13.7% was not grouped with any of the reference variants.
Conclusions: This is the first time that variants of LMP1-EBV have been identified in Cali, Colombia. Additional studies are necessary to characterize the unidentified variant and to determine if it is pathogenic or if it is just an isolate present in the city of Cali.
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References
Epstein MA, Achong BG, Barr YM. Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet. 1964;1:702-3. https://doi.org/10.1016/S0140-6736(64)91524-7
Rickinson A, Kieff E. Epstein Barr virus. In: Knipe DM, Howley PM, editors. Fields virology. 5th edition. Philadelphia: Lippincott Williams & Wilkins; 2007. p. 2655-700.
Higgins CD, Swerdlow AJ, Macsween KF, Harrison N, Williamns H, McAulay K, et al. A study of risk factors for acquisition of Epstein-Barr virus and its subtypes. J Infect Dis. 2007;195:474-82. https://doi.org/10.1086/510854
Pagano J. Is Epstein-Barr virus transmitted sexually? J Infect Dis. 2007;195:469-70. https://doi.org/10.1086/510861
Grünewald K, Desai P, Winkler D, Heymann J, Belnap D, Baumeister W, et al. Threedimensional structure of herpes simplex virus from cryo-electron tomography. Science. 2003;302:1396-8. https://doi.org/10.1126/science.1090284
Sample J, Young L, Martin B, Chatman T, Kieff E, Rickinson A, et al. Epstein-Barr virus types 1 and 2 differ in their EBNA-3A, EBNA-3B, and EBNA-3C genes. J Virol. 1990;64:4084-92.
Chang CM, Yu KJ, Mbulaiteye SM, Hildesheim A, Bhatia K. The extent of genetic diversity of Epstein-Barr virus and its geographic and disease patterns: A need for reappraisal. Virus Res. 2009;143:209-21. https://doi.org/10.1016/j.virusres.2009.07.005
Chabay P, Preciado MV. Epidemiology of Epstein-Barr virus-associated pediatric lymphomas from Argentina. Bol Med Hosp Infant Mex. 2016;73:47-54. https://doi.org/10.1016/j.bmhimx.2015.12.002
Gallart-Catalá A. Infecciones por el virus de Epstein-Barr: mononucleosis infecciosa. 9ª edición. Madrid: Editorial Tratado de Pediatría; 2006. p. 449-55.
Trastoy R, Costa J, Rodríguez J, Navarro D, Barbeito G, Aguilera A. Primoinfección por el virus Epstein-Barr entre los años 2006 a 2015 en el área sanitaria de Santiago de Compostela. Relación con edad y sexo. Rev Esp Quimioter. 2017;30:468-71.
Young L, Murray P. Epstein-Barr virus and oncogenesis: From latent genes to tumours. Oncogene. 2003;22:5108-21. https://doi.org/10.1038/sj.onc.1206556
Niedobitek G, Meru N, Delecluse H. Epstein-Barr virus infection and human malignancies. Int J Exp Pathol. 2001;82:149-70. https://doi.org/10.1111/j.1365-2613.2001.iep190.x
Chang Y, Moore PS, Weiss RA. Human oncogenic viruses: Nature and Discovery. Philos Trans R Soc Lond B Biol Sci. 2017;372:1732-8. https://doi.org/10.1098/rstb.2016.0264
Medina-Ortega A, López-Valencia D, Mosquera-Monje S, Mora-Obando D, Dueñas-Cuéllar A. Virus de Epstein-Barr y su relación con el desarrollo del cáncer. Iatreia. 2017;30:131-45. https://doi.org/10.17533/udea.iatreia.v30n2a03
Tsao SW, Tsang CM, Lo KW. Epstein-Barr virus infection and nasopharyngeal carcinoma. Philos Trans R Soc Lond B Biol Sci. 2017;19:372. https://doi.org/10.1098/rstb.2016.0270
Lorenzetti MA, Gantuz M, Altcheh J, De Matteo E, Chabay P, Preciado M. Distinctive Epstein-Barr virus variants associated with benign and malignant pediatric pathologies: LMP1 sequence characterization and linkage with other viral gene polymorphisms. J Clin Microbiol. 2012;50:609-18. https://doi.org/10.1128/JCM.05778-11
Gantuz M. Identificación y caracterización molecular y funcional de variantes de la proteína latente de membrana 1 del virus de Epstein Barr (tesis). Buenos Aires: Universidad de Buenos Aires; 2016. Fecha de consulta: 20 de septiembre de 2018. Disponible en: https://bibliotecadigital.exactas.uba.ar/download/tesis/tesis_n6055_Gantuz.pdf
Izumi K, Kaye K, Kieff E. The Epstein-Barr virus LMP1 amino acid sequence that engages tumor necrosis factor receptor associated factors is critical for primary B lymphocyte growth transformation. Proc Natl Acad Sci USA.1997;94:1447-52. https://doi.org/10.1073/pnas.94.4.1447
Young LS, Rickinson AB. Epstein-Barr virus: 40 years on. Nat Rev Cancer. 2004;4:757-68. https://doi.org/10.1038/nrc1452
Holthusen K, Talaty P, Everly DN Jr. Regulation of latent membrane protein 1 signaling through interaction with cytoskeletal. J Virol. 2015;89:7277-90. https://doi.org/10.1128/JVI.00321-15
Tsao SW, Tramoutanis G, Dawson CW, Lo AK, Huang DP. The significance of LMP1 expression in nasopharyngeal carcinoma. Semin Cancer Biol. 2002;12:473-87.
https://doi.org/10.1016/s1044579x02000901
Dawson C, Port R, Young L. The role of the EBV-encoded latent membrane proteins LMP1 and LMP2 in the pathogenesis of nasopharyngeal carcinoma (NPC). Semin Cancer Biol. 2012;22:144-53. https://doi.org/10.1016/j.semcancer.2012.01.004
Kieser A, Sterz KR. The latent membrane protein 1 (LMP1). Curr Top Microbiol Immunol. 2015;391:119-49. https://doi.org/10.1007/978-3-319-22834-1_4
Vaysberg MO, Hatton SL, Lambert AL, Snow B, Wong SM, Krams S, et al. Tumor-derived variants of Epstein-Barr virus latent membrane protein 1 induce sustained Erk activation and c-Fos. J Biol Chem. 2008;283:36573-85. https://doi.org/10.1074/jbc.M802968200
Tzellos S, Farrell P. Epstein-Barr virus sequence variation - biology and disease. Pathogens. 2012;1:156-174. https://doi.org/10.3390/pathogens1020156
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. https://doi.org/10.1006/viro.1999.9855
Hatfull G, Bankier AT, Barrell BG, Farrell PJ. Sequence analysis of Raji Epstein-Barr virus DNA. Virology. 1988;164:334-40.
Dolan A, Addison C, Gatherer D, Davison AJ, McGeoch DJ. The genome of Epstein-Barr virus type 2 Strain AG876. Virology. 2006;350:164-70. https://doi.org/10.1016/j.virol.2006.01.015
Lei H, Li T, Hung G, Li B, Tsai S, Lo S. Identification and characterization of EBV genomes in spontaneously immortalized human peripheral blood B lymphocytes by NGS technology. BMC Genomics. 2013;14:804. https://doi.org/10.1186/1471-2164-14-804
Santpere G, Darre F, Blanco S, Alcami A, Villoslada P, Mar AB, et al. Genome-wide analysis of wild-type Epstein-Barr virus genomes derived from healthy individuals of the 1,000 Genomes Project. Genome Biol Evol. 2014;6:846-60. https://doi.org/10.1093/gbe/evu054
Giraldo-Ocampo S, Osorio JC, Fernández A, Castillo A. Detección del virus Epstein Barr en escolares adolescentes en la ciudad de Cali, Colombia. Infectio. 2019;23:175-81. https://doi.org/10.22354/in.v23i2.775
Kingman DW, Weiss WB, Jaffe ES, Kumar S, Frekko K, Raffeld M. Epstein-Barr virus latent membrane protein-1 oncogene deletions: Correlations with malignancy in Epstein-Barr virus associated lymphoproliferative disorders and malignant lymphomas. Blood.1996;88:242-51.
Zuo L, Yu H, Liu L, Tang Y, Wu H, Yang J, et al. The copy number of Epstein-Barr virus latent genome correlates with the oncogenicity by the activation level of LMP1 and NF-kB. Oncotarget. 2015;6:41033-44. https://doi.org/10.18632/oncotarget.5708
Kumar S, Stecher G, Tamura K. MEGA 7: Molecular Evolutionary Genetics Analysis version 7.0. Mol Biol Evol. 2016;33:1870-4. https://doi.org/10.1093/molbev/msw054
Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res.1994;22:4673-80. https://doi.org/10.1093/nar/22.22.4673
Coleman C, Daud I, Ogolla S, Ritchie J, Smith N, Sumba P, et al. Epstein-Barr virus type 2 infects t cells in healthy Kenyan children. J Infect Dis. 2017;216:670-7. https://doi.org/10.1093/infdis/jix363
Palser A, Grayson N, White R, Corton C, Correia S, Ba Abdullah M, et al Genome diversity of Epstein-Barr virus from multiple tumour types and normal infection. J Virol. 2015;89:5222-37. https://doi.org/10.1128/JVI.03614-14
Chabay P, De Matteo E, Merediz A, Preciado M. High frequency of Epstein Barr virus latent membrane protein-1 30 bp deletion in a series of pediatric malignancies in Argentina. Arch Virol. 2004;149:1515-26. https://doi.org/10.1007/s00705-004-0311-1
Correa R, Fellner M, Alonio L, Durand K, Teyssie A, Picconi M. Epstein-Barr virus (EBV) in healthy carriers: Distribution of genotypes and 30 bp deletion in latent membrane protein-1 (LMP-1) oncogene. J Med Virol. 2004;73:583-8. https://doi.org/10.1002/jmv.20129
Ai JH, Xie ZD, Liu CY, Gao LW, Yan J. Characteristic of nuclear antigen 1 gene and latent membrane protein 1 gene of Epstein-Barr virus in primary EBV infection in children in Beijin area in 2005-2010. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2012;26:352-5.
Feederle R, Klinke O, Kutikhin A, Poirey R, Tsai MH, Delecluse HJ. Epstein-Barr virus: From the detection of sequence polymorphisms to the recognition of viral types. Curr Top Microbiol Immunol. 2015;390:119-48. https://doi.org/10.1007/978-3-319-22822-8_7
Chiara M, Manzari C, Lionetti C, Mechelli R, Anastasiadou E, Chiara M. et al. Geographic population structure in Epstein-Barr virus revealed by comparative genomics. Genome Biol Evol. 2016;8:3284-91. https://doi.org/10.1093/gbe/evw226
Smatti M, Yassine H, Abudeh R, AlMarawani A, Taleb S, Althani A, et al. Prevalence and molecular profiling of Epstein Barr virus (EBV) among healthy blood donors from different nationalities in Qatar. PLoS One. 2017;12:e0189033. https://doi.org/10.1371/journal.pone.0189033
Saechan V, Settheetham-Ishida W, Kimura R, Tiwawech D, Mitarnun W, Ishida T. Epstein-Barr virus strains defined by the latent membrane protein 1 sequence characterize Thai ethnic groups. J Gen Virol. 2010;9:2054-61. https://doi.org/10.1099/vir.0.021105-0
Gantuz M, Lorenzetti MA, Chabay PA, Preciado M. A novel recombinant variant of latent membrane protein 1 from Epstein Barr virus in Argentina denotes phylogeographical association. PLoS One. 2017;10:1059-62. https://doi.org/10.1371/journal.pone.0174221
Karpova M, Schoumans J, Blennow E, Ernberg I, Henter J, Smirnov A, et al. Combined spectral karyotyping, comparative genomic hybridization, and in vitro apoptyping of a panel of Burkitt’s lymphoma-derived B cell lines reveals an unexpected complexity of chromosomal aberrations and a recurrence of specific abnormalities in chemoresistant cell lines. Int J Oncol. 2006;26:605-17. https://doi.org/10.3892/ijo.28.3.605
Liao HM, Liu H, Lei H, Li B, Chin PJ, et al. Frequency of EBV LMP-1 promoter and coding variations in Burkitt lymphoma samples in Africa and South America and peripheral blood in Uganda. Cancers (Basel). 2018;10:177. https://doi.org/10.3390/cancers10060177
Carrascal E, Koriyama C, Akiba S, Tamayo O, Itoh T, Eizuru Y, et al. Epstein-Barr virusassociated gastric carcinoma in Cali, Colombia. Oncol Rep. 2003;10:1059-62. https://doi.org/10.3892/or.10.4.1059
Mesa J, Aristizábal B. Seguimiento con carga viral para virus Epstein-Barr en pacientes pediátricos con trasplante hepático. Médicas UIS. 2015;28:393-401. https://doi.org/10.18273/revmed.v28n3-2015015
Zuercher E, Butticaz C, Wyniger J, Martínez R, Battegay M, Boffi El, et al. Genetic diversity of EBV-encoded LMP1 in the Swiss HIV cohort study and implication for NF-Kb activation. PloS One. 2012;7:e32168. https://doi.org/10.1371/journal.pone.0032168
Nagamine M, Takahara M, Kishibe K, Nagat T, Ishii H, Bandoh N et al. Sequence variations of Epstein-Barr virus LMP1 gene in nasal NK/Tcell lymphoma. Virus Genes. 2007;34:47–54. https://doi.org/10.1007/s11262-006-0008-5
Senyuta N, Yakovleva L, Goncharova E, Scherback L, Diduk S, Smirnova K, et al. Epstein-Barr virus latent membrane protein 1 polymorphism in nasopharyngeal carcinoma and other oral cavity tumors in Russia. J Med Virol. 2014;86:290-300. https://doi.org/10.1002/jmv.23729
Yakovleva L, Senyuta N, Goncharova E, Scherback L, Smirnova R, Pavlish O, et al. Epstein-Barr virus lmp1 oncogene variants in cell lines of different origin. Mol Biol (Mosk). 2015;49:714-22. https://doi.org/10.7868/S0026898415050213
Pavlish OA, Diduk SV, Smirnova KV, Shcherbak LN, Goncharova EV, Shalginskykh NA, et al. Mutations of the Epstein-Barr virus LMP1 gene in Russian patients with lymphoid pathology and healthy individuals. Vopr Virusol. 2008;53:10-6.
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