Natural Variation of Epstein-Barr Virus Genes, Proteins, and Primary MicroRNA.
Natural Variation of Epstein-Barr Virus Genes, Proteins, and Primary MicroRNA.
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DOI：
10.1128/jvi.00375-17
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发表时间：
2017-08-01
影响因子：
5.4
通讯作者：
Farrell PJ
中科院分区：
文献类型：
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作者：
Correia S;Palser A;Elgueta Karstegl C;Middeldorp JM;Ramayanti O;Cohen JI;Hildesheim A;Fellner MD;Wiels J;White RE;Kellam P;Farrell PJ
来自大约 200 个 Epstein-Barr 病毒 (EBV) 毒株（包括许多初级分离株）的病毒基因序列已被用于研究关键病毒遗传区域的变异，特别是 LMP1、Zp、gp350、EBNA1 和 BART microRNA (miRNA) 簇 2。对来自不同地理和种族背景的人的唾液样本中 1 型和 2 型 EBV 进行测定表明，健康白种人中只占一小部分英国人主要携带 2 型 EBV。 Zp 和 gp350 变体与 2 型 EBV 的连锁可能是由于它们的基因邻近 EBNA3 基因座，这是 1 型/2 型区别的主要决定因素之一。 EBNA1 DNA 结合域的新分类称为 QCIGP，是对其蛋白质序列进行系统发育分析的结果，但与 1 型/2 型分类无关。通过成熟 miRNA 序列之外的初级 miRNA 中的单核苷酸多态性 (SNP)，BART 簇 2 miRNA 区域分为三个主要变体。这些 SNP 可能会导致中国和印度尼西亚鼻咽癌 (NPC) 样本中常见的 BART 变体的一些 miRNA 的表达水平发生变化。这里鉴定的 EBV 遗传变异为未来对特定 EBV 变异与 EBV 生物学和 EBV 相关疾病的关联进行更直接的分析提供了基础。重要性 与 EBV 相关的疾病的发病率在世界不同地区差异很大。因此，EBV基因组序列变异与宿主的健康、疾病、地理和种族之间的关系对于理解EBV在疾病中的作用和开发有效的EBV疫苗可能很重要。本文对与这些疾病相关的特定 EBV 基因变异进行了迄今为止最全面的分析，并提出了 EBV 疫苗。通过关注 LMP1、Zp、gp350、EBNA1 和 BART miRNA 簇 2 的变异，证明了与已知 1 型/2 型菌株的新关系，并提出了 EBNA1 和 BART miRNA 的新分类。
Viral gene sequences from an enlarged set of about 200 Epstein-Barr virus (EBV) strains, including many primary isolates, have been used to investigate variation in key viral genetic regions, particularly LMP1, Zp, gp350, EBNA1, and the BART microRNA (miRNA) cluster 2. Determination of type 1 and type 2 EBV in saliva samples from people from a wide range of geographic and ethnic backgrounds demonstrates a small percentage of healthy white Caucasian British people carrying predominantly type 2 EBV. Linkage of Zp and gp350 variants to type 2 EBV is likely to be due to their genes being adjacent to the EBNA3 locus, which is one of the major determinants of the type 1/type 2 distinction. A novel classification of EBNA1 DNA binding domains, named QCIGP, results from phylogeny analysis of their protein sequences but is not linked to the type 1/type 2 classification. The BART cluster 2 miRNA region is classified into three major variants through single-nucleotide polymorphisms (SNPs) in the primary miRNA outside the mature miRNA sequences. These SNPs can result in altered levels of expression of some miRNAs from the BART variant frequently present in Chinese and Indonesian nasopharyngeal carcinoma (NPC) samples. The EBV genetic variants identified here provide a basis for future, more directed analysis of association of specific EBV variations with EBV biology and EBV-associated diseases. IMPORTANCE Incidence of diseases associated with EBV varies greatly in different parts of the world. Thus, relationships between EBV genome sequence variation and health, disease, geography, and ethnicity of the host may be important for understanding the role of EBV in diseases and for development of an effective EBV vaccine. This paper provides the most comprehensive analysis so far of variation in specific EBV genes relevant to these diseases and proposed EBV vaccines. By focusing on variation in LMP1, Zp, gp350, EBNA1, and the BART miRNA cluster 2, new relationships with the known type 1/type 2 strains are demonstrated, and a novel classification of EBNA1 and the BART miRNAs is proposed.