Tu Chaofeng, Zeng Zhaoyang, Qi Peng, Li Xiayu, Yu Zhengyuan, Guo Can, Xiong Fang, Xiang Bo, Zhou Ming, Gong Zhaojian, Liao Qianjin, Yu Jianjun, He Yi, Zhang Wenling, Li Xiaoling, Li Yong, Li Guiyuan, Xiong Wei
The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, China.
The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
J Virol. 2017 Aug 10;91(17). doi: 10.1128/JVI.00301-17. Print 2017 Sep 1.
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 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. 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.
爱泼斯坦-巴尔病毒（EBV）是一种普遍存在的γ疱疹病毒，在几乎所有人群中都高度流行，并与许多人类癌症相关，如鼻咽癌（NPC）、霍奇金病和胃癌。然而，在这些与EBV相关的癌症中，只有鼻咽癌表现出显著的种族和地理分布差异。我们推测EBV基因组变异可能在不同地理区域的不同人类癌症发病机制中发挥作用。在本研究中，我们从中国南方的湖南省收集了18份鼻咽癌活检标本，并组装了18个源自鼻咽癌活检标本的EBV（NPC-EBV）基因组，命名为HN1至HN18。这是通过杂交靶向富集EBV DNA，然后进行二代测序来揭示序列多样性实现的。与EBV参考基因组相比，这些EBV基因组总共存在20570个变异，包括20328个替换、88个插入和154个缺失。系统发育分析表明，所有NPC-EBV基因组均与其他EBV基因组不同。此外，HN1至HN18在EBV基因中存在一些非同义变异，包括编码潜伏、早期裂解和被膜蛋白的基因，如LMP1跨膜结构域1和3内的替换、ENBA1的FoP重复和zf-AD结构域，此外非编码区域也存在畸变，尤其是在BamHI A向右转录的微小RNA中。这些变异可能具有潜在的生物学意义。总之，我们报道了从湖南省原发性鼻咽癌活检标本中分离出的EBV全基因组序列变异情况。这可能有助于进一步了解基因组变异如何促进致癌作用，进而影响EBV相关癌症的治疗。鼻咽癌（NPC）与爱泼斯坦-巴尔病毒（EBV）感染高度相关，并表现出显著的种族和地理分布差异。中国南方的湖南省鼻咽癌发病率较高。在此，我们报告了从该地区原发性鼻咽癌活检标本中分离出的病毒的18个新型EBV基因组序列，揭示了全基因组序列多样性。
