Contribución de los tipos y variantes de virus Epstein-Barr (EBV) a la detección temprana de los desórdenes linfoproliferativos post-trasplante (PTLD)
Epstein-Barr virus (EBV) infection is widely distributed in the world and produces a\npersistent infection in B lymphocytes. It is associated with the development of benign and\nmalignant pathologies, including Post-Lymphoproliferative Disorders (PTLD) in transplant patients.\nAccording to genomic h...
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| Formato: | Tesis de maestría acceptedVersion |
| Lenguaje: | Español |
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Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica
2024
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_7816 https://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_7816.dir/7816.PDF |
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| Sumario: | Epstein-Barr virus (EBV) infection is widely distributed in the world and produces a\npersistent infection in B lymphocytes. It is associated with the development of benign and\nmalignant pathologies, including Post-Lymphoproliferative Disorders (PTLD) in transplant patients.\nAccording to genomic heterogeneity, EBV has been classified into viral types (EBV-1 and EBV-2)\nand genetic variants, among them those encoding the EBNA-1 and LMP-1 proteins. Analysis of\nviral genetic variability could identify strains that contribute to the development of PTLD or that\nonly reflect local geographic circulation. The objective of this study was to analyze the genetic\ndiversity of EBV and its relationship with the development of PTLD.\nA cross-sectional study was carried out in the anatomical compartments of viral\npersistence, in which tonsils samples and peripheral blood mononuclear cells (PBMC) from a\npediatric population were analyzed, including: 57 non-transplanted children (Non-Tx), 44\ntransplanted recipients (Tx) and 52 transplanted patients with histological diagnosis of PTLD (Tx-\nPTLD). In addition, an exploratory study on the frequency of appearance of genetic variability was\nperformed: PBMC, which had been taken during the follow-up of 10 transplant patients, 5 of\nwhom developed PTLD, were analyzed. EBV-1 and EBV-2 types and variants in EBNA-1 and LMP-1\nwere determined using PCR/sequencing strategies.\nIn all the groups studied, both viral types were detected, with a frequency of EBV-1\ngreater than 80% and a higher presence of coinfection (EBV-1 + EBV-2) in the Tx and Tx-PTLD\ngroups. The EBNA-1 variants in decreasing frequency were: V-leu, P-thr, P-ala, and V-ala. Four\nnew sub-variants were described (V-ala (I), V-leu (I), V-leu Ag (I), V-leu Ag (II)). A wide variability in\nLMP-1 was described, with a variant of China-1 (China-1*) being the only one detected in Non-Tx\nand the predominant one in Tx and Tx-PTLD. There were no differences in the distribution of viral\ntypes, nor in the EBNA-1 or LMP-1 variants among the groups of children studied (p>0.05), nor\nbetween the anatomical compartments of viral persistence (p>0.05).\nIn the follow-up analysis, the same viral type and EBNA-1 variant was observed in the Tx\ngroup (EBV-1 and EBNA-1V-leu), while before the diagnosis of PTLD, EBV-2 and/or or the EBNA-\n1P-thr variant was identified.\nPTLD would not be associated with a specific pattern of variability, although EBV-2 or\nEBNA-1P-thr could indicate a trend towards their development. In our region, the predominant\nviral type and variants in EBNA-1 and LMP-1 would be EBV-1, V-leu and China-1*. Viral types and\nvariants do not show compartmentalization at the anatomical sites of viral persistence.\nInformation is provided that could be relevant for the implementation of future vaccines and/or\nspecific treatments in relation to PTLD and other EBV associated diseases. |
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