Oncovirology Laboratory, Division of Specialized Laboratories, Instituto Nacional de Câncer (INCA), Rio de Janeiro 20230-130, RJ, Brazil.
Stem Cell Laboratory, Division of Specialized Laboratories, Instituto Nacional de Câncer (INCA), Rio de Janeiro 20230-130, RJ, Brazil.
Int J Mol Sci. 2024 May 3;25(9):5002. doi: 10.3390/ijms25095002.
Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus etiologically associated with benign and malignant diseases. Since the pathogenic mechanisms of EBV are not fully understood, understanding EBV genetic diversity is an ongoing goal. Therefore, the present work describes the genetic diversity of the lytic gene in a sampling of 70 EBV-positive cases from southeastern Brazil. Additionally, together with the genetic regions previously characterized, the aim of the present study was to determine the impact of viral genetic factors that may influence EBV genetic diversity. Accordingly, the phylogenetic analysis of the indicated two main clades with high support, BZ-A and BZ-B (PP > 0.85). Thus, the BZ-A clade was the most diverse clade associated with the main polymorphisms investigated, including the haplotype Type 1 + V3 ( < 0.001). Furthermore, the multigene phylogenetic analysis (MLA) between and the oncogene showed specific clusters, revealing haplotypic segregation that previous single-gene phylogenies from both genes failed to demonstrate. Surprisingly, the Raji-related variant clusters were shown to be more diverse, associated with BZ-A/B and the Type 2/1 + V3 haplotypes. Finally, due to the high haplotypic diversity of the Raji-related variants, the number of DNA recombination-inducing motifs (DRIMs) was evaluated within the different clusters defined by the MLA. Similarly, the haplotype BZ-A + Raji was shown to harbor a greater number of DRIMs ( < 0.001). These results call attention to the high haplotype diversity of EBV in southeast Brazil and strengthen the hypothesis of the recombinant potential of South American Raji-related variants via the oncogene.
EB 病毒(EBV)是一种普遍存在的γ疱疹病毒,与良性和恶性疾病有病因学关联。由于 EBV 的发病机制尚未完全了解,因此了解 EBV 的遗传多样性是一个持续的目标。因此,本工作描述了来自巴西南部的 70 例 EBV 阳性病例中裂解基因的遗传多样性。此外,与先前表征的遗传区域一起,本研究的目的是确定可能影响 EBV 遗传多样性的病毒遗传因素的影响。因此,对的系统发育分析表明存在两个主要的分支,支持度很高,分别为 BZ-A 和 BZ-B(PP>0.85)。因此,BZ-A 分支是与主要研究的多态性相关的最多样化的分支,包括单倍型 1+V3(<0.001)。此外,和致癌基因之间的多基因系统发育分析(MLA)显示出特定的聚类,揭示了单基因系统发育分析未能证明的单倍型分离。令人惊讶的是,Raji 相关变体聚类显示出更高的多样性,与 BZ-A/B 和 2/1+V3 单倍型相关。最后,由于 Raji 相关变体的高单倍型多样性,评估了不同聚类内的 DNA 重组诱导基序(DRIMs)的数量,这些聚类是由 MLA 定义的。同样,BZ-A+Raji 单倍型被证明含有更多的 DRIMs(<0.001)。这些结果引起了对巴西南部 EBV 高单倍型多样性的关注,并通过致癌基因加强了南美的 Raji 相关变体的重组潜力假说。