Essential role of inverted repeat in Epstein-Barr virus IR-1 in B cell transformation; geographical variation of the viral genome

Essential role of inverted repeat in Epstein-Barr virus IR-1 in B cell transformation; geographical variation of the viral genome
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DOI:
10.1098/rstb.2018.0299
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发表时间:
2019-05-27
影响因子:
6.3
通讯作者:
Farrell, Paul J.
Farrell, Paul J.
中科院分区:
生物学1区
文献类型:
--
作者:
Bridges, Ray;Correia, Samantha;Farrell, Paul J.

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EB病毒(EBV)基因组的许多区域,重复和独特的序列,有助于菌株之间观察到的地理变异。在这里,我们使用了一个大的策划EBV基因组序列的比对,以确定1型EBV毒株基因组中的主要变异位点;潜伏膜蛋白1(LMP 1)中的CAO缺失是世界各地EBV毒株独特区域中最常见的主要插入缺失。主成分分析用于鉴定序列变异模式和核苷酸位置,以区分来自不同地理区域的EBV。病毒基因组序列变异也影响遗传内容的解释;已知基因、复制起点和基因表达控制区解释了病毒基因组的大部分,但仍有一些功能未知的部分。这些EBV基因组区域之一包含IR-1主要内部重复序列阵列内的大反向重复序列(invR)。我们删除了这个invR序列,并表明这废除了病毒的能力,将人类B细胞转化为淋巴母细胞样细胞line.This文章的一部分,主题问题“沉默的癌症代理人:多学科建模的人类DNA肿瘤病毒”。
Many regions of the Epstein-Barr virus (EBV) genome, repeated and unique sequences, contribute to the geographical variation observed between strains. Here we use a large alignment of curated EBV genome sequences to identify major sites of variation in the genome of type 1 EBV strains; the CAO deletion in latent membrane protein 1 (LMP1) is the most frequent major indel present in the unique regions of EBV strains from various parts of the world. Principal component analysis was used to identify patterns of sequence variation and nucleotide positions in the sequences that can distinguish EBV from some different geographical regions. Viral genome sequence variation also affects interpretation of genetic content; known genes, origins of replication and gene expression control regions explain most of the viral genome but there are still a few sections of unknown function. One of these EBV genome regions contains a large inverted repeat sequence (invR) within the IR-1 major internal repeat array. We deleted this invR sequence and showed that this abolished the ability of the virus to transform human B cells into lymphoblastoid cell lines.This article is part of the theme issue 'Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses'.