Cargando…

Non-Random Pattern of Integration for Epstein-Barr Virus with Preference for Gene-Poor Genomic Chromosomal Regions into the Genome of Burkitt Lymphoma Cell Lines

Background: Epstein-Barr virus (EBV) is an oncogenic virus found in about 95% of endemic Burkitt lymphoma (BL) cases. In latently infected cells, EBV DNA is mostly maintained in episomal form, but it can also be integrated into the host genome, or both forms can coexist in the infected cells. Method...

Descripción completa

Detalles Bibliográficos
Autores principales: Janjetovic, Snjezana, Hinke, Juliane, Balachandran, Saranya, Akyüz, Nuray, Behrmann, Petra, Bokemeyer, Carsten, Dierlamm, Judith, Murga Penas, Eva Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781420/
https://www.ncbi.nlm.nih.gov/pubmed/35062290
http://dx.doi.org/10.3390/v14010086
_version_ 1784638082026307584
author Janjetovic, Snjezana
Hinke, Juliane
Balachandran, Saranya
Akyüz, Nuray
Behrmann, Petra
Bokemeyer, Carsten
Dierlamm, Judith
Murga Penas, Eva Maria
author_facet Janjetovic, Snjezana
Hinke, Juliane
Balachandran, Saranya
Akyüz, Nuray
Behrmann, Petra
Bokemeyer, Carsten
Dierlamm, Judith
Murga Penas, Eva Maria
author_sort Janjetovic, Snjezana
collection PubMed
description Background: Epstein-Barr virus (EBV) is an oncogenic virus found in about 95% of endemic Burkitt lymphoma (BL) cases. In latently infected cells, EBV DNA is mostly maintained in episomal form, but it can also be integrated into the host genome, or both forms can coexist in the infected cells. Methods: In this study, we mapped the chromosomal integration sites of EBV (EBV-IS) into the genome of 21 EBV+ BL cell lines (BL-CL) using metaphase fluorescence in situ hybridization (FISH). The data were used to investigate the EBV-IS distribution pattern in BL-CL, its relation to the genome instability, and to assess its association to common fragile sites and episomes. Results: We detected a total of 459 EBV-IS integrated into multiple genome localizations with a preference for gene-poor chromosomes. We did not observe any preferential affinity of EBV to integrate into common and rare fragile sites or enrichment of EBV-IS at the chromosomal breakpoints of the BL-CL analyzed here, as other DNA viruses do. Conclusions: We identified a non-random integration pattern into 13 cytobands, of which eight overlap with the EBV-IS in EBV-transformed lymphoblastoid cell lines and with a preference for gene- and CpGs-poor G-positive cytobands. Moreover, it has been demonstrated that the episomal form of EBV interacts in a non-random manner with gene-poor and AT-rich regions in EBV+ cell lines, which may explain the observed affinity for G-positive cytobands in the EBV integration process. Our results provide new insights into the patterns of EBV integration in BL-CL at the chromosomal level, revealing an unexpected connection between the episomal and integrated forms of EBV.
format Online
Article
Text
id pubmed-8781420
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-87814202022-01-22 Non-Random Pattern of Integration for Epstein-Barr Virus with Preference for Gene-Poor Genomic Chromosomal Regions into the Genome of Burkitt Lymphoma Cell Lines Janjetovic, Snjezana Hinke, Juliane Balachandran, Saranya Akyüz, Nuray Behrmann, Petra Bokemeyer, Carsten Dierlamm, Judith Murga Penas, Eva Maria Viruses Article Background: Epstein-Barr virus (EBV) is an oncogenic virus found in about 95% of endemic Burkitt lymphoma (BL) cases. In latently infected cells, EBV DNA is mostly maintained in episomal form, but it can also be integrated into the host genome, or both forms can coexist in the infected cells. Methods: In this study, we mapped the chromosomal integration sites of EBV (EBV-IS) into the genome of 21 EBV+ BL cell lines (BL-CL) using metaphase fluorescence in situ hybridization (FISH). The data were used to investigate the EBV-IS distribution pattern in BL-CL, its relation to the genome instability, and to assess its association to common fragile sites and episomes. Results: We detected a total of 459 EBV-IS integrated into multiple genome localizations with a preference for gene-poor chromosomes. We did not observe any preferential affinity of EBV to integrate into common and rare fragile sites or enrichment of EBV-IS at the chromosomal breakpoints of the BL-CL analyzed here, as other DNA viruses do. Conclusions: We identified a non-random integration pattern into 13 cytobands, of which eight overlap with the EBV-IS in EBV-transformed lymphoblastoid cell lines and with a preference for gene- and CpGs-poor G-positive cytobands. Moreover, it has been demonstrated that the episomal form of EBV interacts in a non-random manner with gene-poor and AT-rich regions in EBV+ cell lines, which may explain the observed affinity for G-positive cytobands in the EBV integration process. Our results provide new insights into the patterns of EBV integration in BL-CL at the chromosomal level, revealing an unexpected connection between the episomal and integrated forms of EBV. MDPI 2022-01-04 /pmc/articles/PMC8781420/ /pubmed/35062290 http://dx.doi.org/10.3390/v14010086 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Janjetovic, Snjezana
Hinke, Juliane
Balachandran, Saranya
Akyüz, Nuray
Behrmann, Petra
Bokemeyer, Carsten
Dierlamm, Judith
Murga Penas, Eva Maria
Non-Random Pattern of Integration for Epstein-Barr Virus with Preference for Gene-Poor Genomic Chromosomal Regions into the Genome of Burkitt Lymphoma Cell Lines
title Non-Random Pattern of Integration for Epstein-Barr Virus with Preference for Gene-Poor Genomic Chromosomal Regions into the Genome of Burkitt Lymphoma Cell Lines
title_full Non-Random Pattern of Integration for Epstein-Barr Virus with Preference for Gene-Poor Genomic Chromosomal Regions into the Genome of Burkitt Lymphoma Cell Lines
title_fullStr Non-Random Pattern of Integration for Epstein-Barr Virus with Preference for Gene-Poor Genomic Chromosomal Regions into the Genome of Burkitt Lymphoma Cell Lines
title_full_unstemmed Non-Random Pattern of Integration for Epstein-Barr Virus with Preference for Gene-Poor Genomic Chromosomal Regions into the Genome of Burkitt Lymphoma Cell Lines
title_short Non-Random Pattern of Integration for Epstein-Barr Virus with Preference for Gene-Poor Genomic Chromosomal Regions into the Genome of Burkitt Lymphoma Cell Lines
title_sort non-random pattern of integration for epstein-barr virus with preference for gene-poor genomic chromosomal regions into the genome of burkitt lymphoma cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781420/
https://www.ncbi.nlm.nih.gov/pubmed/35062290
http://dx.doi.org/10.3390/v14010086
work_keys_str_mv AT janjetovicsnjezana nonrandompatternofintegrationforepsteinbarrviruswithpreferenceforgenepoorgenomicchromosomalregionsintothegenomeofburkittlymphomacelllines
AT hinkejuliane nonrandompatternofintegrationforepsteinbarrviruswithpreferenceforgenepoorgenomicchromosomalregionsintothegenomeofburkittlymphomacelllines
AT balachandransaranya nonrandompatternofintegrationforepsteinbarrviruswithpreferenceforgenepoorgenomicchromosomalregionsintothegenomeofburkittlymphomacelllines
AT akyuznuray nonrandompatternofintegrationforepsteinbarrviruswithpreferenceforgenepoorgenomicchromosomalregionsintothegenomeofburkittlymphomacelllines
AT behrmannpetra nonrandompatternofintegrationforepsteinbarrviruswithpreferenceforgenepoorgenomicchromosomalregionsintothegenomeofburkittlymphomacelllines
AT bokemeyercarsten nonrandompatternofintegrationforepsteinbarrviruswithpreferenceforgenepoorgenomicchromosomalregionsintothegenomeofburkittlymphomacelllines
AT dierlammjudith nonrandompatternofintegrationforepsteinbarrviruswithpreferenceforgenepoorgenomicchromosomalregionsintothegenomeofburkittlymphomacelllines
AT murgapenasevamaria nonrandompatternofintegrationforepsteinbarrviruswithpreferenceforgenepoorgenomicchromosomalregionsintothegenomeofburkittlymphomacelllines