Epstein–Barr virus gene polymorphisms in Chinese Hodgkin’s disease cases and healthy donors: identification of three distinct virus variants

Abstract

Epstein-Barr virus (EBV) is associated with several malignancies. Specific EBV gene variants, e.g. the BamHI f configuration, a C-terminal region 30 bp deletion in the latent membrane protein-1 (LMP1) gene (del-LMP) and the loss of an XhoI site in LMP1 (XhoI-loss), are found in Chinese cases of nasopharyngeal carcinoma (NPC), suggesting that EBV sequence variation may be involved in oncogenesis. In order to understand better the epidemiology of these EBV variants, they were studied in virus isolates from EBV-positive Chinese cases of Hodgkin's disease (HD ; n l 71) and donor throat washings from healthy Chinese. Sequencing was performed of 15 representative EBV isolates, including the first analysis of the LMP1 promoter in Asian wild-type EBV isolates. The following observations were made. (i) Three EBV LMP1 variants were identified, designated Chinese groups (CG) 1-3. In both EBV-associated HD and in healthy Chinese, CG1-like viruses showing del-LMP1 and XhoI-loss were predominant. (ii) CG1 viruses were distinct from European and African variants, suggesting that this profile is useful for epidemiological studies. (iii) Specific patterns of mutations were present in the LMP1 promoter in both CG1 and CG2. (iv) The BamHI f variant was not found in Chinese HD, in contrast to Chinese NPC and European HD. This study confirms that EBV isolates in Chinese HD and other tumours differ from those reported in Western cases. However, this reflects the predominant virus strain present in the healthy Chinese population, suggesting that these are geographically restricted polymorphisms rather than tumour-specific strains.

Analysis of the Bcl-2 and p53 protein expression in the lymphoproliferative lesions in the upper Egypt

“…This slight female predilection in NHL may be related to the repeated blood transfusions during deliveries, which carry the risk of viral infections and transmission of chemical carcinogens. 16 In accordance with previous studies 12 HD had male predilection. This finding could be explained by the prevalence EBV infection in males than in females.…”

Comparative analysis of oncogenic properties and nuclear factor- B activity of latent membrane protein 1 natural variants from Hodgkin's lymphoma's Reed-Sternberg cells and normal B-lymphocytes

“…33 Subsequent to this initial report, numerous LMP1-variants from both nasopharyngeal carcinomas and Hodgkin's lymphomas have been described by various groups. [34][35][36] However, to our knowledge, results published in the literature fail to demonstrate direct associations between any single LMP1-variant and any specific EBV-associated disease. [34][35][36] Based on phylogenetic analysis, Nancy Raab-Traub's group proposed classifing LMP1 natural variants into seven distinct strains, and showed a bias regarding the frequency of some LMP1 strains and nasopharyngeal carcinomas, suggesting a potential selection pressure on these variants during epithelial cell oncogenesis.…”

“…[34][35][36] However, to our knowledge, results published in the literature fail to demonstrate direct associations between any single LMP1-variant and any specific EBV-associated disease. [34][35][36] Based on phylogenetic analysis, Nancy Raab-Traub's group proposed classifing LMP1 natural variants into seven distinct strains, and showed a bias regarding the frequency of some LMP1 strains and nasopharyngeal carcinomas, suggesting a potential selection pressure on these variants during epithelial cell oncogenesis. 24 Our previous analysis of the LMP1 polymorphism in both Reed-Sternberg cells and normal Blymphocytes from Hodgkin's lymphomas clearly suggested an intra-host diversity for the two viral strains from a common viral ancestor and showed that LMP1-variants in tumor cells are highly mutated when compared to LMP1-variants from healthy donors.…”

Epstein–barr Virus in the Population of Two Geographically Different Regions of Russia

“…и дополнительно 26 аминокислотных замен [1]. Доказано, что функционально LMP1-Сао по сравнению с LMP1-В95.8 обладает более вы-раженным трансформирующим потенциалом in vitro [19], а также повышенной туморогенно-стью, сниженной иммуногенностью и усилен-ной сигнальной активностью [1,15,22]. Пока-зано также, что нуклеотидные замены в генах, кодирующих различные варианты LMP1, как правило, расположены в областях, контролиру-ющих стадии транскрипции или трансляции.…”

“…Пока-зано также, что нуклеотидные замены в генах, кодирующих различные варианты LMP1, как правило, расположены в областях, контролиру-ющих стадии транскрипции или трансляции. В составе белка -это аминокислоты, которые влияют на функциональную активность, им-муногенность, время полужизни или трансфор-мирующий потенциал LMP1 [15,22]. Актива-ция LMP1 целого ряда транскрипционных фак-торов (NF-κB, AP-1, STAT) изменяет профиль внутриклеточной активности ряда сигнальных путей [20].…”