Genome-Wide Analysis of 18 Epstein-Barr Viruses Isolated from Primary Nasopharyngeal Carcinoma Biopsy Specimens
Genome-Wide Analysis of 18 Epstein-Barr Viruses Isolated from Primary Nasopharyngeal Carcinoma Biopsy Specimens
复制标题
从原发性鼻咽癌活检标本中分离出的 18 种 Epstein-Barr 病毒的全基因组分析
DOI：
10.1128/jvi.00301-17
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发表时间：
2017-09-01
影响因子：
5.4
通讯作者：
Xiong, Wei
中科院分区：
文献类型：
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作者：
Tu, Chaofeng;Zeng, Zhaoyang;Xiong, Wei
摘要 Epstein-Barr 病毒 (EBV) 是一种普遍存在的伽马疱疹病毒，几乎在所有人群中都非常流行，并且与许多人类癌症相关，例如鼻咽癌 (NPC)、霍奇金病和胃癌。然而，在这些 EBV 相关癌症中，只有 NPC 表现出显着的种族和地理分布。我们假设 EBV 基因组变异可能导致不同地理区域不同人类癌症的发病机制。在这项研究中，我们从中国南部湖南省收集了 18 个鼻咽癌活检标本，并从头组装了 18 个鼻咽癌活检标本衍生的 EBV (NPC-EBV) 基因组，命名为 HN1 至 HN18。这是通过杂交对 EBV DNA 进行目标富集，然后进行新一代测序以揭示序列多样性来实现的。与EBV参考基因组相比，这些EBV基因组总共包含20,570个变异，包括20,328个替换、88个插入和154个缺失。系统发育分析表明，所有 NPC-EBV 基因组均不同于其他 EBV 基因组。此外，HN1至HN18在EBV基因中具有一些非同义变异，包括编码潜伏蛋白、早期裂解蛋白和被膜蛋白的基因，例如LMP1的跨膜结构域1和3、FoP_重复和ENBA1的zf-AD结构域内的替换，以及非编码区的畸变，特别是在BamHI A向右转录物中 微小RNA。这些变异可能具有潜在的生物学意义。总之，我们报告了从湖南省获得的原发性鼻咽癌活检标本中分离出的 EBV 序列变异的全基因组视图。这可能有助于进一步了解基因组变异如何导致致癌，从而影响 EB 病毒相关癌症的治疗。重要性 鼻咽癌 (NPC) 与 Epstein-Barr 病毒 (EBV) 感染高度相关，并表现出显着的种族和地理分布。中国南方的湖南省是鼻咽癌的高发地区。在这里，我们报告了 18 个新的 EBV 基因组序列，这些序列来自从该地区的原发性 NPC 活检标本中分离出的病毒，揭示了全基因组序列的多样性。
ABSTRACT Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that is highly prevalent in almost all human populations and is associated with many human cancers, such as nasopharyngeal carcinoma (NPC), Hodgkin's disease, and gastric carcinoma. However, in these EBV-associated cancers, only NPC exhibits remarkable ethnic and geographic distribution. We hypothesized that EBV genomic variations might contribute to the pathogenesis of different human cancers in different geographic areas. In this study, we collected 18 NPC biopsy specimens from the Hunan Province in southern China and de novo assembled 18 NPC biopsy specimen-derived EBV (NPC-EBV) genomes, designated HN1 to HN18. This was achieved through target enrichment of EBV DNA by hybridization, followed by next-generation sequencing, to reveal sequence diversity. These EBV genomes harbored 20,570 variations totally, including 20,328 substitutions, 88 insertions, and 154 deletions, compared to the EBV reference genome. Phylogenetic analysis revealed that all NPC-EBV genomes were distinct from other EBV genomes. Furthermore, HN1 to HN18 had some nonsynonymous variations in EBV genes including genes encoding latent, early lytic, and tegument proteins, such as substitutions within transmembrane domains 1 and 3 of LMP1, FoP_duplication, and zf-AD domains of ENBA1, in addition to aberrations in noncoding regions, especially in BamHI A rightward transcript microRNAs. These variations might have potential biological significance. In conclusion, we reported a genome-wide view of sequence variation in EBV isolated from primary NPC biopsy specimens obtained from the Hunan Province. This might contribute to further understanding of how genomic variations contribute to carcinogenesis, which would impact the treatment of EBV-associated cancer. IMPORTANCE Nasopharyngeal carcinoma (NPC) is highly associated with Epstein-Barr virus (EBV) infection and exhibits remarkable ethnic and geographic distribution. Hunan Province in southern China has a high incidence rate of NPCs. Here, we report 18 novel EBV genome sequences from viruses isolated from primary NPC biopsy specimens in this region, revealing whole-genome sequence diversity.