Epstein–Barr Virus Genetic Variation in Lymphoblastoid Cell Lines Derived from Kenyan Pediatric Population

Simbiri, Kenneth O; Smith, Nicholas A.; Otieno, RO; Wohlford, Eric E. M.; Daud, Ibrahim; Odada, Sumba P.; Middleton, Frank A.; Rochford, Rosemary

doi:10.1371/journal.pone.0125420

Cited by 18 publications

(15 citation statements)

References 41 publications

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“…The single strain in group 3, when compared with the other subtype 1 strains, showed it was not closely related to those in the other groups. These findings corroborate those in a Kenyan study [ 48 ]. This suggests that inter and intra-genetic variations in EBV genomes exist, and that within a geographical region different EBV genetic strains can coexist [ 48 , 49 ].…”

Section: Discussionsupporting

confidence: 92%

“…These findings corroborate those in a Kenyan study [ 48 ]. This suggests that inter and intra-genetic variations in EBV genomes exist, and that within a geographical region different EBV genetic strains can coexist [ 48 , 49 ]. However, a study conducted in the United Kingdom, which examined EBV strains from different geographical locations, showed that strains from the same region clustered together as opposed to those from different regions [ 49 ].…”

Section: Discussionsupporting

confidence: 92%

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Evidence of EBV infection in lymphomas diagnosed in Lusaka, Zambia

Kafita¹,

Kaile²,

Malyangu³

et al. 2018

Pan Afr Med J

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IntroductionEpstein-Barr virus (EBV) is a ubiquitous virus that infects more than 90% of the world's population, and is implicated in lymphoma pathogenesis. However, in Zambia during the diagnosis of these lymphomas, the association of the virus with the lymphomas is not established. Since most patients with lymphomas have poor prognosis, the identification of the virus within the lymphoma lesion will allow for more targeted therapy. The aim of this study was to provide evidence of the presence of the EBV in lymphomas diagnosed at the University Teaching Hospital (UTH) in Lusaka, Zambia.MethodsOne hundred and fifty archival formalin-fixed paraffin embedded suspected lymphoma tissues stored over a 4-year period in the Histopathology Laboratory at the UTH in Lusaka, Zambia, were analysed. Histological methods were used to identify the lymphomas, and the virus was detected using Polymerase Chain Reaction (PCR). Subtyping of the virus was achieved through DNA sequencing of the EBNA-2 region of the viral genome. Chi square or fisher's exact test was used to evaluate the association between EBV status, type of lymphoma and gender.ResultsThe majority of the lymphomas identified were non-Hodgkin's lymphoma (NHL) (80%) followed by Hodgkin's lymphoma (HL) (20%). EBV was detected in 51.8% of the cases, 54.5% of which were associated with NHL cases, while 40.9% associated with HL cases. The predominant subtype of the virus in both types of lymphomas was subtype 1. One of the lymphoma cases harboured both subtype 1 and 2 of the virus.ConclusionThis study showed that EBV is closely associated with lymphomas. Therefore, providing evidence of the presence of the virus in lymphoma tissues will aid in targeted therapy. To our knowledge this is the first time such data has been generated in Zambia.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Evidence of EBV infection in lymphomas diagnosed in Lusaka, Zambia

Kafita¹,

Kaile²,

Malyangu³

et al. 2018

Pan Afr Med J

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“…A clonal LMP1 gene containing a 30 bp deletion (del30) was found in 46.1% of NK/T cell lymphomas and only in 4.8% of the controls, with much worse patient survival in those with this deletion . However, as shown in endemic Burkitt lymphoma, within a geographic region, different EBV genetic variations can coexist, such that specific gene variation associations with presentation or prognosis have been difficult. Although our study was not powered to detect individual variants associated with survival or PTLD type, we have demonstrated the technology can be successfully be used for this approach.…”

Section: Discussionmentioning

confidence: 86%

Metagenomic analysis of DNA viruses from posttransplant lymphoproliferative disorders

et al. 2019

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Posttransplant lymphoproliferative disorders (PTLDs), 50%‐80% of which are strongly associated with Epstein‐Barr virus (EBV), carry a high morbidity and mortality. Most clinical/epidemiological/tumor characteristics do not consistently associate with worse patient survival, so our aim was to identify if other viral genomic characteristics associated better with survival. We extracted DNA from stored paraffin‐embedded PTLD tissues at our center, identified viral sequences by metagenomic shotgun sequencing (MSS), and analyzed the data in relation to clinical outcomes. Our study population comprised 69 PTLD tissue samples collected between 1991 and 2015 from 60 subjects. Nucleotide sequences from at least one virus were detected by MSS in 86% (59/69) of the tissues (EBV in 61%, anelloviruses 52%, gammapapillomaviruses 14%, CMV 7%, and HSV in 3%). No viruses were present in higher proportion in EBV‐negative PTLD (compared to EBV‐positive PTLD). In univariable analysis, death within 5 years of PTLD diagnosis was associated with anellovirus (P = 0.037) and gammapapillomavirus (P = 0.036) detection by MSS, higher tissue qPCR levels of the predominant human anellovirus species torque teno virus (TTV; P = 0.016), T cell type PTLD, liver, brain or bone marrow location. In multivariable analyses, T cell PTLD (P = 0.006) and TTV PCR level (P = 0.012) remained significant. In EBV‐positive PTLD, EBNA‐LP, EBNA1 and EBNA3C had significantly higher levels of nonsynonymous gene variants compared to the other EBV genes. Multiple viruses are detectable in PTLD tissues by MSS. Anellovirus positivity, not EBV positivity,was associated with worse patient survival in our series. Confirmation and extension of this work in larger multicenter studies is desirable.

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“…As much as 90% of total usable reads were mapped to type 1 EBV reference, hence, signified how PCR enrichment can greatly increase cost-effectiveness in determination of the viral sequence. Similarly, the EBVs of spontaneous LCLs established from peripheral blood mononuclear cells (PBMC) of four Kenyan children were PCR-amplified by using 59 pairs of primer [ 26 ]. The pooled PCR products were sequenced by Illumina MiSeq platform, and there were more than 90% of reads in each sample could be aligned to reference EBV genome.…”

Section: Next-generation Sequencing Of Ebv Genomesmentioning

confidence: 99%

From Conventional to Next Generation Sequencing of Epstein-Barr Virus Genomes

Kwok

Chiang

2016

Viruses

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Genomic sequences of Epstein–Barr virus (EBV) have been of interest because the virus is associated with cancers, such as nasopharyngeal carcinoma, and conditions such as infectious mononucleosis. The progress of whole-genome EBV sequencing has been limited by the inefficiency and cost of the first-generation sequencing technology. With the advancement of next-generation sequencing (NGS) and target enrichment strategies, increasing number of EBV genomes has been published. These genomes were sequenced using different approaches, either with or without EBV DNA enrichment. This review provides an overview of the EBV genomes published to date, and a description of the sequencing technology and bioinformatic analyses employed in generating these sequences. We further explored ways through which the quality of sequencing data can be improved, such as using DNA oligos for capture hybridization, and longer insert size and read length in the sequencing runs. These advances will enable large-scale genomic sequencing of EBV which will facilitate a better understanding of the genetic variations of EBV in different geographic regions and discovery of potentially pathogenic variants in specific diseases.

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Epstein–Barr Virus Genetic Variation in Lymphoblastoid Cell Lines Derived from Kenyan Pediatric Population

Cited by 18 publications

References 41 publications

Evidence of EBV infection in lymphomas diagnosed in Lusaka, Zambia

Evidence of EBV infection in lymphomas diagnosed in Lusaka, Zambia

Metagenomic analysis of DNA viruses from posttransplant lymphoproliferative disorders

From Conventional to Next Generation Sequencing of Epstein-Barr Virus Genomes

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