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Abstract：
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 BZLF1 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 BZLF1 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 (p < 0.001). Furthermore, the multigene phylogenetic analysis (MLA) between BZLF1 and the oncogene LMP1 showed specific clusters, revealing haplotypic segregation that previous single-gene phylogenies from both genes failed to demonstrate. Surprisingly, the LMP1 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 (p < 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 LMP1 oncogene.
摘要：
爱泼斯坦-巴尔病毒（EBV）是一种广泛存在的γ疱疹病毒，在病因上与良性和恶性疾病有关。由于EBV的致病机制尚未完全了解，了解EBV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东南部的70例EBV阳性病例中裂解基因BZLF1的遗传多样性。此外,连同先前表征的遗传区域，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，BZLF1的系统发育分析表明有两个具有高支持的主要进化枝，BZ-A和BZ-B(PP>0.85)。因此，BZ-A进化枝是与所研究的主要多态性相关的最多样化的进化枝，包括单倍型1+V3(p<0.001)。此外，BZLF1和癌基因LMP1之间的多基因系统发育分析（MLA）显示出特定的簇，揭示了单倍型分离，这两个基因先前的单基因系统发育未能证明。令人惊讶的是,LMP1与Raji相关的变异簇显示出更多的多样性，与BZ-A/B和2/1+V3单倍型相关。最后,由于Raji相关变异的高度单倍型多样性，在MLA定义的不同簇中评估了DNA重组诱导基序(DRIM)的数量.同样，单倍型BZ-A+Raji显示含有更多数量的DRIM(p<0.001)。这些结果引起了人们对巴西东南部EBV的高单倍型多样性的关注，并加强了通过LMP1癌基因对南美Raji相关变体的重组潜力的假设。
