The extent of genetic diversity of Epstein-Barr virus and its geographic and disease patterns: A need for reappraisal

Chang, Cindy M.; Yu, Kelly J.; Mbulaiteye, Sam M.; Hildesheim, Allan; Bhatia, Kishor

doi:10.1016/j.virusres.2009.07.005

Cited by 197 publications

(271 citation statements)

References 144 publications

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“…Type B EBV without LMP1 deletion can only effectively transform B cells in immunodeficient patients, as has been shown in HIV þ patients. 16,21,22 This evidence strongly suggests that this patient might have had a more profound immunosuppression than the presumed age-related immune dysfunction. In our experience, EBNA2 expression in EBV þ diffuse large B-cell lymphoma of the elderly is rather rare.…”

Section: Discussionmentioning

confidence: 84%

Geographic variation in the prevalence of Epstein–Barr virus-positive diffuse large B-cell lymphoma of the elderly: a comparative analysis of a Mexican and a German population

et al. 2011

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Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma of the elderly was included as a provisional entity in the 2008 WHO lymphoma classification. Most reports of this disease come from Asia and little is known about it in other regions of the world, including Latin America. Therefore, in this study, 305 diffuse large B-cell lymphomas in patients above 50 years were analyzed, 136 from Mexico and 169 from Germany. EBV was detected by Epstein-Barr early RNA (EBER) in situ hybridization. Only cases with EBER þ in the majority of tumor cells were regarded as EBV þ diffuse large B-cell lymphoma. The prevalence of EBV þ diffuse large B-cell lymphoma in Mexican patients was found to be 7% (9 of 136), whereas only 2% (4 of 169) of the German cases were positive. The median age at diagnosis was 66 years in the Mexican cohort, as opposed to 77 years in the German group. The site of presentation was in both groups predominantly nodal in nine cases (70%) and extranodal in four cases (30%). Of the 13 EBV þ cases, 10 (77%) were classified as polymorphic and 3 (23%) as monomorphic type. The polymorphic cases showed a non-germinal center B-cell immunophenotype (CD10À MUM1 þ ). Twelve cases (92%) were LMP1 positive and two (15%) expressed EBNA2. An interesting finding was the high frequency of EBV type B with the LMP1 30 bp deletion found in the Mexican cases (50%). Eight of the 11 evaluable cases were B-cell monoclonal by polymerase chain reaction. In summary, we found a similar prevalence of EBV þ diffuse large B-cell lymphoma of the elderly in a Mexican population compared with what has been reported in Asian countries, and in contrast to the low frequency in Western populations (1-3%). However, compared with the Asian series, the Mexican patients were younger at diagnosis, presented predominantly with nodal disease and rarely expressed EBNA2 protein.Modern Pathology (2011Pathology ( ) 24, 1046Pathology ( -1054 doi:10.1038/modpathol.2011 published online 15 April 2011 Keywords: EBV; elderly; large cell lymphoma; Mexico Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that infects 490% of the human population establishing persistent latent infection in the host. 1Although EBV infection is benign in most individuals, it has been linked to the etiology of a rather broad spectrum of B-cell lymphoproliferations both

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Section: Discussionmentioning

confidence: 84%

Geographic variation in the prevalence of Epstein–Barr virus-positive diffuse large B-cell lymphoma of the elderly: a comparative analysis of a Mexican and a German population

et al. 2011

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“…1 The potential pathogenic role of EBV genetic variants in MS may be in keeping with epidemiologic observations, in particular the geographic gradient of MS and the change in MS risk in migrants, 2 and with the reported association between virus genetic variants and EBV-related malignancies with different geographic distribution. [3][4][5] Also, the discrepancy between the global diffusion of EBV infection and the low prevalence of MS could be at least in part explained by EBV genomic diversity that differently affects MS development.…”

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confidence: 99%

Epstein-Barr virus genetic variants are associated with multiple sclerosis

et al. 2015

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Objective: We analyzed the Epstein-Barr nuclear antigen 2 (EBNA2) gene, which contains the most variable region of the viral genome, in persons with multiple sclerosis (MS) and control subjects to verify whether virus genetic variants are involved in disease development. 84-14.32; p 5 0.016) and underrepresentation of 1.3B allele (OR 5 0.23; 95% CI 0.08-0.51; p 5 0.0006). We identified new genetic variants, mostly 1.2 allele-and MS-associated (especially amino acid variation at position 245; OR 5 9.4; 95% CI 1.19-78.72; p 5 0.0123). In all cases, the consensus sequence from deep sequencing confirmed Sanger sequencing (including the cosegregation of newly identified variants with known EBNA2 alleles) and showed that the extent of genotype intraindividual variability was higher than expected: rare EBNA2 variants were detected in all HDs and patients with MS (range 1-17 and 3-19, respectively). EBNA2 variants did not seem to correlate with human leucocyte antigen typing or clinical/MRI features. MethodsConclusions: Our study unveils a strong association between Epstein-Barr virus genomic variants and MS, reinforcing the idea that Epstein-Barr virus contributes to disease development. Despite converging evidence supporting an etiologic role for Epstein-Barr virus (EBV) in multiple sclerosis (MS), we still do not know through which mechanisms the virus may contribute to disease development. 1 The potential pathogenic role of EBV genetic variants in MS may be in keeping with epidemiologic observations, in particular the geographic gradient of MS and the change in MS risk in migrants, 2 and with the reported association between virus genetic variants and EBV-related malignancies with different geographic distribution.3-5 Also, the discrepancy between the global diffusion of EBV infection and the low prevalence of MS could be at least in part explained by EBV genomic diversity that differently affects MS development.Major methodologic difficulties hinder the study of EBV variants through sequencing of the whole viral genome. To date, only 8 complete genome sequences have been described: 5 from patients with EBV-related diseases and 3 from healthy individuals.6 This is mainly attributable

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“…Среди последних особое место занимает рак носоглотки (РНГ), в возникнове-нии которого ВЭБ играет ключевую роль, стимулируя прогрессирование патологического процесса от пред-раковых поражений до появления злокачественной опухоли [2]. Заболеваемость РНГ в мире характеризу-ется географической и этнической вариабельностью [3]. Она наиболее высокая в южных провинциях Китая и странах Юго-Восточной Азии (25-30 случаев на 100 000 населения в год), несколько ниже -в араб-ских странах Северной Африки, в Гренландии и у эскимосов на Аляске [4].…”

Section: том 2 экспериментальные статьи 57unclassified

Diagnostic significance of DNA and antibodies against capsid antigens of anti-Epstein–Barr virus antibodies levels in blood plasma of nasopharyngeal carcinoma patients from non-endemic region

Gurtsevitch¹,

Сенюта²,

Кондратова³

et al. 2015

Usp. mol. onkol

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The extent of genetic diversity of Epstein-Barr virus and its geographic and disease patterns: A need for reappraisal

Cited by 197 publications

References 144 publications

Geographic variation in the prevalence of Epstein–Barr virus-positive diffuse large B-cell lymphoma of the elderly: a comparative analysis of a Mexican and a German population

Geographic variation in the prevalence of Epstein–Barr virus-positive diffuse large B-cell lymphoma of the elderly: a comparative analysis of a Mexican and a German population

Epstein-Barr virus genetic variants are associated with multiple sclerosis

Diagnostic significance of DNA and antibodies against capsid antigens of anti-Epstein–Barr virus antibodies levels in blood plasma of nasopharyngeal carcinoma patients from non-endemic region

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