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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Autor principal:	Torrá, Florencia Lucía
Otros Autores:	Picconi, María Alejandra
Formato:	Tesis de maestría acceptedVersion
Lenguaje:	Español
Publicado:	Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica 2024
Materias:	Epstein-Barr Desórdenes linfoproliferativos post-trasplante Variabilidad genética Tipos virales Variantes de EBNA-1 y LMP-1 Post-transplant lymphoproliferative disorders Genetic variability Viral types EBNA-1 and LMP-1 variants Ciencias de la vida
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
Aporte de:	Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires

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institution	Universidad de Buenos Aires
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collection	Repositorio Digital de la Universidad de Buenos Aires (UBA)
language	Español
orig_language_str_mv	spa
topic	Epstein-Barr Desórdenes linfoproliferativos post-trasplante Variabilidad genética Tipos virales Variantes de EBNA-1 y LMP-1 Epstein-Barr Post-transplant lymphoproliferative disorders Genetic variability Viral types EBNA-1 and LMP-1 variants Ciencias de la vida
spellingShingle	Epstein-Barr Desórdenes linfoproliferativos post-trasplante Variabilidad genética Tipos virales Variantes de EBNA-1 y LMP-1 Epstein-Barr Post-transplant lymphoproliferative disorders Genetic variability Viral types EBNA-1 and LMP-1 variants Ciencias de la vida Torrá, Florencia Lucía Contribución de los tipos y variantes de virus Epstein-Barr (EBV) a la detección temprana de los desórdenes linfoproliferativos post-trasplante (PTLD)
topic_facet	Epstein-Barr Desórdenes linfoproliferativos post-trasplante Variabilidad genética Tipos virales Variantes de EBNA-1 y LMP-1 Epstein-Barr Post-transplant lymphoproliferative disorders Genetic variability Viral types EBNA-1 and LMP-1 variants Ciencias de la vida
description	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.
author2	Picconi, María Alejandra
author_facet	Picconi, María Alejandra Torrá, Florencia Lucía
format	Tesis de maestría Tesis de maestría acceptedVersion
author	Torrá, Florencia Lucía
author_sort	Torrá, Florencia Lucía
title	Contribución de los tipos y variantes de virus Epstein-Barr (EBV) a la detección temprana de los desórdenes linfoproliferativos post-trasplante (PTLD)
title_short	Contribución de los tipos y variantes de virus Epstein-Barr (EBV) a la detección temprana de los desórdenes linfoproliferativos post-trasplante (PTLD)
title_full	Contribución de los tipos y variantes de virus Epstein-Barr (EBV) a la detección temprana de los desórdenes linfoproliferativos post-trasplante (PTLD)
title_fullStr	Contribución de los tipos y variantes de virus Epstein-Barr (EBV) a la detección temprana de los desórdenes linfoproliferativos post-trasplante (PTLD)
title_full_unstemmed	Contribución de los tipos y variantes de virus Epstein-Barr (EBV) a la detección temprana de los desórdenes linfoproliferativos post-trasplante (PTLD)
title_sort	contribución de los tipos y variantes de virus epstein-barr (ebv) a la detección temprana de los desórdenes linfoproliferativos post-trasplante (ptld)
publisher	Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica
publishDate	2024
url	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
work_keys_str_mv	AT torraflorencialucia contribuciondelostiposyvariantesdevirusepsteinbarrebvaladetecciontempranadelosdesordeneslinfoproliferativosposttrasplanteptld
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spelling	I28-R145-HWA_78162025-06-12 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. Fil: Torrá, Florencia Lucía. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Buenos Aires, Argentina Picconi, María Alejandra Fellner, María Dolores Torrá, Florencia Lucía 2024-02-26 La infección por el virus Epstein-Barr (EBV) se halla ampliamente distribuida en el mundo y\nproduce una infección persistente en linfocitos B. Se asocia al desarrollo de patologías benignas y\nmalignas, entre ellas en pacientes trasplantados puede provocar el desarrollo de Desórdenes\nLinfoproliferativos Post-trasplante (PTLD). De acuerdo a la heterogeneidad genómica el EBV ha\nsido clasificado en tipos virales (EBV-1 y EBV-2) y variantes genéticas, entre ellas las que codifican\na las proteínas EBNA-1 y LMP-1. El análisis de la variabilidad genética viral podría identificar cepas\nque contribuyen al desarrollo de PTLD o que sólo reflejen la circulación geográfica local. El\nobjetivo de esta tesis fue analizar la diversidad genética del EBV y su relación con el desarrollo de\nPTLD.\nSe realizó un estudio transversal en los compartimientos anatómicos de persistencia viral, en\nel cual se analizaron muestras de amígdalas y células mononucleares periféricas (CMP) de 57 no\ntrasplantados (No-Tx), 44 trasplantados (Tx) y 52 trasplantados con diagnóstico histológico de\nPTLD (Tx-PTLD). Además, se efectuó un estudio exploratorio sobre la frecuencia de aparición de\nvariabilidad genética: se analizaron CMP tomadas durante el seguimiento de 10 pacientes\ntrasplantados, 5 de los cuales desarrollaron PTLD. Los tipos EBV-1 y EBV-2 y las variantes en EBNA-\n1 y LMP-1 se determinaron utilizando estrategias de PCR/secuenciación.\nEn todos los grupos estudiados se detectó a ambos tipos virales, con una frecuencia del EBV-1\nsuperior al 80% y mayor presencia de coinfección (EBV-1 + EBV-2) en los grupos Tx y Tx-PTLD. Las\nvariantes de EBNA-1 en frecuencia decreciente fueron: V-leu, P-thr, P-ala, y V-ala. Se describieron\n4 nuevas sub-variantes (V-ala (I), V- leu (I), V-leu Ag (I), V-leu Ag (II)). Se describió una amplia\nvariabilidad en LMP-1, siendo una variante de China-1 (China-1) la única detectada en No-Tx y la\npredominante en Tx y Tx-PTLD. No hubo diferencias en la distribución de los tipos virales, ni en las\nvariantes EBNA-1 o LMP-1 entre los grupos niños estudiados (p>0.05), ni entre los\ncompartimentos anatómicos de persistencia viral (p>0.05).\nEn el análisis de seguimiento, se observó el mismo tipo viral y variante de EBNA-1 en el grupo\nTx (EBV-1 y EBNA-1V-leu), mientras que antes del diagnóstico de PTLD, se identificó al EBV-2 y/o a la\nvariante EBNA-1P-thr.\nLos PTLDs no se asociarían con un patrón de variabilidad específico, aunque el EBV-2 o EBNA-\n1P-thr podrían indicar una tendencia a su desarrollo. En nuestra región, el tipo viral y las variantes\nen EBNA-1 y LMP-1 predominantes serían EBV-1, V-leu y China-1. Los tipos y variantes virales no\nmuestran compartimentalización en los sitios anatómicos de persistencia viral. Se aporta\nconocimiento que podría ser relevante para la implementación de futuras vacunas y/o\ntratamientos específicos en relación a los PTLDs y a otras enfermedades asociadas a EBV. application/pdf Cavallaro, Lucía V. Preciado, María Victoria Giordano, Mirta Epstein-Barr Desórdenes linfoproliferativos post-trasplante Variabilidad genética Tipos virales Variantes de EBNA-1 y LMP-1 Epstein-Barr Post-transplant lymphoproliferative disorders Genetic variability Viral types EBNA-1 and LMP-1 variants spa Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Ciencias de la vida Magíster de la Universidad de Buenos Aires en Biología Molecular Médica Contribución de los tipos y variantes de virus Epstein-Barr (EBV) a la detección temprana de los desórdenes linfoproliferativos post-trasplante (PTLD) info:eu-repo/semantics/masterThesis info:ar-repo/semantics/tesis de maestría info:eu-repo/semantics/acceptedVersion 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

Contribución de los tipos y variantes de virus Epstein-Barr (EBV) a la detección temprana de los desórdenes linfoproliferativos post-trasplante (PTLD)

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