Hoelzer Karin, Shackelton Laura A, Parrish Colin R
Baker Institute for Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Nucleic Acids Res. 2008 May;36(9):2825-37. doi: 10.1093/nar/gkn121. Epub 2008 Mar 26.
Nucleotide composition varies greatly among DNA viruses of animals, yet the evolutionary pressures and biological mechanisms driving these patterns are unclear. One of the most striking discrepancies lies in the frequency of CpG (the dinucleotide CG, linked by a phosphate group), which is underrepresented in most small DNA viruses (those with genomes below 10 kb) but not in larger DNA viruses. Cytosine methylation might be partially responsible, but research on this topic has focused on a few virus groups. For several viruses that integrate their genome into the host genome, the methylation status during this stage has been studied extensively, and the relationship between methylation and viral-induced tumor formation has been examined carefully. However, for actively replicating viruses--particularly small DNA viruses--the methylation status of CpG motifs is rarely known and the effects on the viral life cycle are obscure. In vertebrate host genomes, most cytosines at CpG sites are methylated, which in vertebrates acts to regulate gene expression and facilitates the recognition of unmethylated, potentially pathogen-associated DNA. Here we briefly introduce cytosine methylation before reviewing what is currently known about CpG methylation in DNA viruses.
动物DNA病毒的核苷酸组成差异很大，然而驱动这些模式的进化压力和生物学机制尚不清楚。最显著的差异之一在于CpG（由磷酸基团连接的二核苷酸CG）的频率，它在大多数小型DNA病毒（基因组小于10 kb的病毒）中含量较低，但在较大的DNA病毒中并非如此。胞嘧啶甲基化可能起到了部分作用，但关于这个主题的研究主要集中在少数病毒群体上。对于几种将基因组整合到宿主基因组中的病毒，这一阶段的甲基化状态已得到广泛研究，并且甲基化与病毒诱导的肿瘤形成之间的关系也已得到仔细研究。然而，对于正在活跃复制的病毒——尤其是小型DNA病毒——CpG基序的甲基化状态鲜为人知，其对病毒生命周期的影响也不清楚。在脊椎动物宿主基因组中，CpG位点的大多数胞嘧啶都发生了甲基化，这在脊椎动物中起到调节基因表达的作用，并有助于识别未甲基化的、可能与病原体相关的DNA。在此，我们在回顾目前已知的DNA病毒中CpG甲基化情况之前，先简要介绍一下胞嘧啶甲基化。
