Laboratório de Oncovirologia, Centro de Transplante de Medula Óssea, Instituto Nacional de Câncer "José Alencar Gomes da Silva" (INCA), Ministério da Saúde, Rio de Janeiro 20230-130, Brazil.
Laboratório de Células Tronco, Centro de Transplante de Medula Óssea, Instituto Nacional de Câncer "José Alencar Gomes da Silva" (INCA), Ministério da Saúde, Rio de Janeiro 20230-130, Brazil.
Viruses. 2022 Aug 12;14(8):1762. doi: 10.3390/v14081762.
Epstein−Barr virus (EBV) is a saliva-borne ɣ-herpesvirus associated with benign and malignant lymphoproliferation. EBV-mediated tumorigenic mechanisms are not fully understood and may be related to viral genetic variations. In this work, we characterize the genetic diversity of EBV from Brazil, assessing 82 samples derived from saliva from asymptomatic carriers (n = 45), biopsies of benign reactive hyperplasia (n = 4), and lymphomas (n = 33). Phylogenetic and phylogeographic analysis of the entire coding region of the LMP-1 was performed. Additionally, type 1/type 2 distinction by the EBNA3C gene and Zp variants were evaluated. Our results revealed a high diversity of EBV in Brazil, with the co-circulation of four main clades, described here as: Mediterranean (40.2%, n = 33), Raji/Argentine (39%, n = 32), B95-8 (6.1%, n = 5), and Asian II (1.2%, n = 1). The Raji/Argentine and Mediterranean clades were the most prevalent in South America (45% and 28%, respectively). The Raji/Argentine clade was associated with polymorphisms I124V/I152L, del30 bp, and ins15 bp (p < 0.0001, to all clades) and with a high haplotype diversity related to EBV type and Zp variants. We found that a Raji/Argentine subclade spread primarily from Brazil and later to other South American countries. Although no LMP1 variant has been directly associated with disease, the Raji/Argentine clade was predominantly clustered with lymphomas (61%) and the Mediterranean clade with non-malignant cases (59%) (p = 0.1). These data highlight the high genetic diversity of EBV circulating in Brazil, calling attention to a Raji-related variant with great recombination potential in Brazilian lymphomas.
EB 病毒（EBV）是一种唾液传播的γ疱疹病毒，与良性和恶性淋巴增生有关。EBV 介导的肿瘤发生机制尚未完全阐明，可能与病毒基因变异有关。在这项工作中，我们对来自巴西的 EBV 进行了遗传多样性分析，评估了 82 个来自无症状携带者唾液样本（n=45）、良性反应性增生活检样本（n=4）和淋巴瘤样本（n=33）。对 LMP-1 的整个编码区进行了系统进化和系统地理学分析。此外，还评估了 EBNA3C 基因和 Zp 变体的 1 型/2 型区分。我们的结果显示，巴西 EBV 具有高度多样性，存在四个主要分支的循环，这里描述为：地中海（40.2%，n=33）、Raji/阿根廷（39%，n=32）、B95-8（6.1%，n=5）和亚洲 II（1.2%，n=1）。Raji/阿根廷和地中海分支在南美洲最为流行（分别为 45%和 28%）。Raji/阿根廷分支与 I124V/I152L、del30bp 和 ins15bp 多态性相关（p<0.0001，所有分支），与 EBV 类型和 Zp 变体相关的高单倍型多样性相关。我们发现，一个主要从巴西传播的 Raji/阿根廷亚分支，后来传播到其他南美国家。尽管没有 LMP1 变体与疾病直接相关，但 Raji/阿根廷分支主要与淋巴瘤（61%）聚集，地中海分支与非恶性病例（59%）聚集（p=0.1）。这些数据突出了巴西循环 EBV 的高遗传多样性，引起了对巴西淋巴瘤中具有强大重组潜力的 Raji 相关变体的关注。
