Simbiri Kenneth O, Smith Nicholas A, Otieno Richard, Wohlford Eric E M, Daud Ibrahim I, Odada Sumba P, Middleton Frank, Rochford Rosemary
Department of Microbiology and Immunology, Upstate Medical University, Syracuse, New York, United States of America.
Maseno University, Maseno, Kenya.
PLoS One. 2015 May 1;10(5):e0125420. doi: 10.1371/journal.pone.0125420. eCollection 2015.
Epstein-Barr virus (EBV) is associated with Burkitt's lymphoma (BL), and in regions of sub-Saharan Africa where endemic BL is common, both the EBV Type 1 (EBV-1) and EBV Type 2 strains (EBV-2) are found. Little is known about genetic variation of EBV strains in areas of sub-Saharan Africa. In the present study, spontaneous lymphoblastoid cell lines (LCLs) were generated from samples obtained from Kenya. Polymerase chain reaction (PCR) amplification of the EBV genome was done using multiple primers and sequenced by next-generation sequencing (NGS). Phylogenetic analyses against the published EBV-1 and EBV-2 strains indicated that one sample, LCL10 was closely related to EBV-2, while the remaining 3 LCL samples were more closely related to EBV-1. Moreover, single nucleotide polymorphism (SNP) analyses showed clustering of LCL variants. We further show by analysis of EBNA-1, BLLF1, BPLF1, and BRRF2 that latent genes are less conserved than lytic genes in these LCLs from a single geographic region. In this study we have shown that NGS is highly useful for deciphering detailed inter and intra-variations in EBV genomes and that within a geographic region different EBV genetic variations can co-exist, the implications of which warrant further investigation. The findings will enhance our understanding of potential pathogenic variants critical to the development and maintenance of EBV-associated malignancies.
爱泼斯坦-巴尔病毒(EBV)与伯基特淋巴瘤(BL)相关,在撒哈拉以南非洲地方性BL常见的地区,可发现1型爱泼斯坦-巴尔病毒(EBV-1)和2型爱泼斯坦-巴尔病毒毒株(EBV-2)。关于撒哈拉以南非洲地区EBV毒株的基因变异知之甚少。在本研究中,从肯尼亚获得的样本中生成了自发淋巴母细胞系(LCLs)。使用多种引物对EBV基因组进行聚合酶链反应(PCR)扩增,并通过下一代测序(NGS)进行测序。针对已发表的EBV-1和EBV-2毒株的系统发育分析表明,一个样本LCL10与EBV-2密切相关,而其余3个LCL样本与EBV-1关系更密切。此外,单核苷酸多态性(SNP)分析显示LCL变异聚类。我们通过对EBNA-1、BLLF1、BPLF1和BRRF2的分析进一步表明,在来自单一地理区域的这些LCL中,潜伏基因的保守性低于裂解基因。在本研究中,我们表明NGS对于解读EBV基因组中详细的种间和种内变异非常有用,并且在一个地理区域内不同的EBV基因变异可以共存,其影响值得进一步研究。这些发现将增强我们对EBV相关恶性肿瘤发生和维持至关重要的潜在致病变异的理解。