scholarly journals 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

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 86
Author(s):  
Snjezana Janjetovic ◽  
Juliane Hinke ◽  
Saranya Balachandran ◽  
Nuray Akyüz ◽  
Petra Behrmann ◽  
...  
Keyword(s):  
Cell Lines ◽  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Genome Instability ◽  
Fragile Sites ◽  
Random Pattern ◽  
Barr Virus ◽  
Integration Pattern ◽  
Infected Cells ◽  
Epstein Barr

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.

scholarly journals Infection of Epstein–Barr Virus in Type III Latency Modulates Biogenesis of Exosomes and the Expression Profile of Exosomal miRNAs in the Burkitt Lymphoma Mutu Cell Lines

Cancers ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 237 ◽  
Author(s):  
Asuka Nanbo ◽  
Harutaka Katano ◽  
Michiyo Kataoka ◽  
Shiho Hoshina ◽  
Tsuyoshi Sekizuka ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Type I ◽  
Type Iii ◽  
Barr Virus ◽  
Ebv Infection ◽  
Latently Infected ◽  
Infected Cells ◽  
Epstein Barr

Infection of Epstein–Barr virus (EBV), a ubiquitous human gamma herpesvirus, is associated with various malignancies in B lymphocytes and epithelial cells. EBV encodes 49 microRNAs in two separated regions, termed the BART and BHRF1 loci. Although accumulating evidence demonstrates that EBV infection regulates the profile of microRNAs in the cells, little is known about the microRNAs in exosomes released from infected cells. Here, we characterized the expression profile of intracellular and exosomal microRNAs in EBV-negative, and two related EBV-infected Burkitt lymphoma cell lines having type I and type III latency by next-generation sequencing. We found that the biogenesis of exosomes is upregulated in type III latently infected cells compared with EBV-negative and type I latently infected cells. We also observed that viral and several specific host microRNAs were predominantly incorporated in the exosomes released from the cells in type III latency. We confirmed that multiple viral microRNAs were transferred to the epithelial cells cocultured with EBV-infected B cells. Our findings indicate that EBV infection, in particular in type III latency, modulates the biogenesis of exosomes and the profile of exosomal microRNAs, potentially contributing to phenotypic changes in cells receiving these exosomes.

scholarly journals Identification of Epstein-Barr Virus RK-BARF0-Interacting Proteins and Characterization of Expression Pattern

2004 ◽  
Vol 78 (23) ◽  
pp. 12848-12856 ◽  
Author(s):  
Natalie J. Thornburg ◽  
Shuichi Kusano ◽  
Nancy Raab-Traub
Keyword(s):  
Cell Lines ◽  
Epstein Barr Virus ◽  
Interacting Proteins ◽  
Cellular Functions ◽  
Barr Virus ◽  
Acid Protein ◽  
Infected Cells ◽  
Epstein Barr ◽  
Endoplasmic Reticulum Targeting

ABSTRACT The Epstein-Barr virus (EBV) BamHI A transcripts are a family of transcripts that are differentially spliced and can be detected in multiple EBV-associated malignancies. Several of the transcripts may encode proteins. One transcript of interest, RK-BARF0, is proposed to encode a 279-amino-acid protein with a possible endoplasmic reticulum-targeting sequence. In this study, the properties of RK-BARF0 were examined through identification of cellular-interacting proteins through yeast two-hybrid analysis and characterization of its expression in EBV-infected cells and tumors. In addition to the interaction previously identified with cellular Notch, it was determined that RK-BARF0 also bound cellular human I-mfa domain-containing protein (HIC), epithelin, and scramblase. An interaction between RK-BARF0 and Notch or epithelin induced proteasome-dependent degradation of Notch and epithelin but not of HIC or scramblase. Low levels of endogenous Notch expression in EBV-positive cell lines may correlate with RK-BARF0 expression. However, a screen of EBV-positive cell lines and tumors with an affinity-purified α-RK-BARF0 antiserum did not consistently detect RK-BARF0. These data suggest that while RK-BARF0 may have important cellular functions during EBV infection, and while the phenotype of EBV-positive cells suggest its expression, RK-BARF0 levels may be too low to detect.

Subcellular localization of the latent membrane protein LMP-1 in Epstein-Barr virus infected cells by immunogold EM

1994 ◽  
Vol 52 ◽  
pp. 248-249
Author(s):  
D. N. Misra ◽  
R. M. Agostini ◽  
E. J. Yunis
Keyword(s):  
Membrane Protein ◽  
Subcellular Localization ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Hodgkin’S Disease ◽  
Burkitt’S Lymphoma ◽  
Latent Membrane Protein ◽  
Barr Virus ◽  
Infected Cells ◽  
Epstein Barr

Epstein-Barr virus (EBV) infection, prevalent in all human populations, is clinically silent in general, but causes infectious mononucleosis in some adolescents and B-lymphocyte proliferative disorders (LPDs) in immunocompromised individuals (e.g. AIDS infected; allograft recipients). EBV is also etiologically associated with African Burkitt’s lymphoma, nasopharyngeal carcinoma, and Hodgkin’s disease. The virus infects B lymphocytes and transforms them into lymphoblastoid cells which proliferate indefinitely in culture. The latently infected cells express an array of EBV gene products including 6 nuclear antigens (EBNAs), terminal proteins LMP-2A and LMP-2B, latent membrane protein LMP-1, and untranslated RNAs EBER 1 and EBER 2. These components are being extensively studied since they are involved in latency or proliferative transformation; LMP-1 has also shown oncogenic properties. In this work, we have used immunogold electron microscopy for precise subcellular localization of LMP-1 in EBV infected cell lines.Two human cell lines, P3HR-1 (Burkitt’s lymphoma) and CCL-113 (Hodgkin’s disease), obtained from ATCC, were grown in RPMI 1640 containing 20% fetal calf serum, 100 U/ml penicillin and 100 μg/ml streptomycin.

scholarly journals Autorepression of Epstein-Barr Virus Nuclear Antigen 1 Expression by Inhibition of Pre-mRNA Processing

2007 ◽  
Vol 82 (4) ◽  
pp. 1679-1687 ◽  
Author(s):  
Mikio Yoshioka ◽  
Michelle M. Crum ◽  
Jeffery T. Sample
Keyword(s):  
Cell Lines ◽  
Epstein Barr Virus ◽  
Rna Binding ◽  
Cytotoxic T Cells ◽  
Nuclear Antigen ◽  
Genome Maintenance ◽  
Barr Virus ◽  
Latently Infected ◽  
Infected Cells ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) latent infection, and its associated oncogenic potential, is dependent on genome maintenance functions of EBV nuclear antigen 1 (EBNA-1), one of six EBNAs expressed from a common promoter (Wp and then Cp) upon infection of naive B cells. Subsequent host-mediated silencing, however, necessitates the expression of EBNA-1 from the EBNA-1-specific promoter Qp to ensure against genome loss during cell division, including EBV-associated malignancy. Here we addressed the mechanism by which EBNA-1 represses Qp through binding downstream of the transcription start site and the role of this autoregulatory function in EBV latency. Our results revealed that EBNA-1 does not inhibit transcription from Qp, as previously predicted, but acts post- or cotranscriptionally to block the processing of primary transcripts. This does not, however, require the RGG motifs responsible for strong but nonspecific RNA binding by EBNA-1. Within isogenic B-cell lines using either Cp/Wp or Qp, EBNA-1 occupancy of Qp is equivalent, suggesting that autoregulation occurs, albeit to different degrees, during full and restricted EBV latency programs. Finally, in cell lines using Cp or Wp for EBNA expression, unprocessed transcripts from Qp are detectable in the absence of corresponding mRNAs, providing further evidence that this novel mechanism of EBNA-1 action functions during latency. This posttranscriptional mechanism of regulation would provide an efficient means to monitor and regulate EBNA-1 expression from Qp, ensuring levels adequate for genome maintenance but, perhaps more importantly, below an immunogenic threshold above which latently infected cells may be at risk for elimination by EBNA-1-specific cytotoxic T cells.

scholarly journals Up-regulation of Lamin A/C Expression in Epstein-Barr Virus Immortalized B Cells and Burkitt Lymphoma Cell Lines of Activated B Cell Phenotype

2016 ◽  
Author(s):  
Ferenc Bánáti ◽  
Anita Koroknai ◽  
Kálmán Szenthe ◽  
Tamás Tereh ◽  
Nóra Kovács ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Cell Phenotype ◽  
Lamin A ◽  
Histone Marks ◽  
Barr Virus ◽  
Epstein Barr

Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA and protein expression in EBV-immortalized lymphoblastoid cell lines (LCLs) and in group III Burkitt lymphoma (BL) lines where hypomethylated first exons were observed with activating histone marks. In most cell lines with low promoter activity a highly methylated first exon could be detected. Our data showed that methylation of the first exon of LMNA was associated with the downregulation of LMNA expression whereas euchromatic histone marks were enriched at active LMNA promoters in EBV-immortalized LCLs. These data suggest a role for viral latency products to activate LMNAp in EBV-infected latency type III B cells in vitro. Expression of lamin A/C may contribute to the establishment of activated B cell phenotype that needs further explorations.

scholarly journals Burkitt Lymphomas Evolve to Escape Dependencies on Epstein-Barr Virus

2021 ◽  
Vol 10 ◽  
Author(s):  
Rebecca L. Hutcheson ◽  
Adityarup Chakravorty ◽  
Bill Sugden
Keyword(s):  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Mutational Analysis ◽  
Mechanistic Studies ◽  
Barr Virus ◽  
Immune Pressure ◽  
Genome Wide ◽  
Viral Genes ◽  
Infected Cells ◽  
Epstein Barr

Epstein–Barr Virus (EBV) can transform B cells and contributes to the development of Burkitt lymphoma and other cancers. Through decades of study, we now recognize that many of the viral genes required to transform cells are not expressed in EBV-positive Burkitt lymphoma (BL) tumors, likely due to the immune pressure exerted on infected cells. This recognition has led to the hypothesis that the loss of expression of these viral genes must be compensated through some mechanisms. Recent progress in genome-wide mutational analysis of tumors provides a wealth of data about the cellular mutations found in EBV-positive BLs. Here, we review common cellular mutations found in these tumors and consider how they may compensate for the viral genes that are no longer expressed. Understanding these mutations and how they may substitute for EBV’s genes and contribute to lymphomagenesis can serve as a launchpad for more mechanistic studies, which will help us navigate the sea of genomic data available today, and direct the discoveries necessary to improve the treatment of EBV-positive BLs.

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