Parvovirus b19 DNA CpG dinucleotide methylation and epigenetic regulation of viral expression.
Parvovirus b19 DNA CpG dinucleotide methylation and epigenetic regulation of viral expression.
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DOI：
10.1371/journal.pone.0033316
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Gallinella G
中科院分区：
文献类型：
--
作者：
Bonvicini F;Manaresi E;Di Furio F;De Falco L;Gallinella G
CpG DNA甲基化是一种主要的表观遗传修饰，在基因表达调控中发挥作用。对于其基因组具有整合到宿主基因组中或作为潜伏附加体维持的能力的DNA病毒，已经发现DNA甲基化的程度与病毒静止之间存在相关性。没有关于细小病毒B19的信息，细小病毒B19是一种人类致病病毒，能够引起溶解性和持续性感染。在细小病毒B19基因组中，反向末端区域显示了基因组CpG岛的所有特征标记，因此我们假设CpG二核苷酸甲基化在病毒基因组表达调控中的作用。通过适当设计的亚硫酸氢盐修饰的DNA定量实时PCR分析，对细小病毒B19 DNA的CpG二核苷酸甲基化进行了分析。CpG甲基化对病毒基因组表达调控的影响首先通过在模型细胞系中转染未甲基化或体外甲基化的病毒DNA来研究，显示病毒DNA的甲基化与病毒基因组的较低表达水平相关。然后，在不同细胞环境中的体外感染过程中，观察到病毒表达和基因组复制的缺乏都与病毒DNA的CpG甲基化水平的增加相关。最后，在活检样本中存在的病毒DNA中记录了CpG甲基化的存在，表明这种表观遗传修饰在自然感染过程中的发生和可能作用。病毒基因组表达调控的表观遗传水平的存在，可能与病毒基因组的沉默相关并有助于病毒在组织中的维持，可能与细小病毒B19相关的不同类型感染的平衡和结果相关。
CpG DNA methylation is one of the main epigenetic modifications playing a role in the control of gene expression. For DNA viruses whose genome has the ability to integrate in the host genome or to maintain as a latent episome, a correlation has been found between the extent of DNA methylation and viral quiescence. No information is available for Parvovirus B19, a human pathogenic virus, which is capable of both lytic and persistent infections. Within Parvovirus B19 genome, the inverted terminal regions display all the characteristic signatures of a genomic CpG island; therefore we hypothesised a role of CpG dinucleotide methylation in the regulation of viral genome expression. The analysis of CpG dinucleotide methylation of Parvovirus B19 DNA was carried out by an aptly designed quantitative real-time PCR assay on bisulfite-modified DNA. The effects of CpG methylation on the regulation of viral genome expression were first investigated by transfection of either unmethylated or in vitro methylated viral DNA in a model cell line, showing that methylation of viral DNA was correlated to lower expression levels of the viral genome. Then, in the course of in vitro infections in different cellular environments, it was observed that absence of viral expression and genome replication were both correlated to increasing levels of CpG methylation of viral DNA. Finally, the presence of CpG methylation was documented in viral DNA present in bioptic samples, indicating the occurrence and a possible role of this epigenetic modification in the course of natural infections. The presence of an epigenetic level of regulation of viral genome expression, possibly correlated to the silencing of the viral genome and contributing to the maintenance of the virus in tissues, can be relevant to the balance and outcome of the different types of infection associated to Parvovirus B19.
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