Honess R W, Gompels U A, Barrell B G, Craxton M, Cameron K R, Staden R, Chang Y N, Hayward G S
Division of Virology, National Institute for Medical Research, Mill Hill, London, U.K.
J Gen Virol. 1989 Apr;70 ( Pt 4):837-55. doi: 10.1099/0022-1317-70-4-837.
The DNA sequences of genomes from G + C-rich and A + T-rich lymphotropic herpesviruses [i.e. gammaherpesviruses; Epstein-Barr virus and herpesvirus saimiri (HVS)] are deficient in CpG dinucleotides and contain an excess of TpG and CpA dinucleotides relative to frequencies predicted from their mononucleotide compositions. In contrast, for sequences from genomes of G + C-rich and A + T-rich neurotropic herpesviruses (i.e. alphaherpesviruses; herpes simplex virus and varicellazoster virus) and human cytomegalovirus (HCMV; a betaherpesvirus) the mean observed frequencies of these dinucleotides are close to those expected from their mononucleotide compositions. Comparisons between DNA sequences that encode proteins conserved in all these viruses also show that sequences of these lymphotropic viruses are CpG-deficient whereas the homologous genes from the neurotropic viruses and the HCMV are not. Analyses of local variations in dinucleotide frequencies reveal some occurrences of clustered CpG dinucleotides in generally deficient genomes (e.g. upstream of the thymidylate synthase gene of HVS) and locally CpG-deficient regions within some generally non-deficient genomes (e.g. the major immediate early genes of human, simian and murine CMVs). A relative deficiency in CpG and an excess of TpG and CpA dinucleotides is a diagnostic feature of higher eukaryotic DNA sequences that have been subjected to methylation of cytosine residues in CpG doublets with the resulting increase in mutations to give TpG (and thereby its complement, CpA). The available evidence implicates the latent genome as the site of methylation of these herpesviruses. We conclude that in the neurotropic herpesviruses the normal latent precursors to infectious progeny are not methylated whereas there is local methylation of the immediate early locus in the latent genomes of CMVs, and the latent genomes of these lymphotropic herpesviruses are extensively methylated.
富含G + C和富含A + T的嗜淋巴细胞疱疹病毒（即γ疱疹病毒；爱泼斯坦-巴尔病毒和猴疱疹病毒）基因组的DNA序列中，CpG二核苷酸缺乏，相对于根据其单核苷酸组成预测的频率，TpG和CpA二核苷酸过量。相比之下，富含G + C和富含A + T的嗜神经疱疹病毒（即α疱疹病毒；单纯疱疹病毒和水痘-带状疱疹病毒）以及人巨细胞病毒（HCMV；一种β疱疹病毒）基因组序列中，这些二核苷酸的平均观察频率接近根据其单核苷酸组成预期的频率。对所有这些病毒中保守的编码蛋白质的DNA序列进行比较也表明，这些嗜淋巴细胞病毒的序列缺乏CpG，而嗜神经病毒和HCMV的同源基因则没有。对二核苷酸频率局部变化的分析揭示，在通常缺乏的基因组中（如HVS胸苷酸合成酶基因上游）存在一些成簇的CpG二核苷酸，以及在一些通常不缺乏的基因组中（如人、猴和鼠CMV的主要立即早期基因）存在局部CpG缺乏区域。CpG相对缺乏以及TpG和CpA二核苷酸过量是高等真核生物DNA序列的一个诊断特征，这些序列中的CpG双联体中的胞嘧啶残基发生了甲基化，导致突变增加，产生TpG（及其互补物CpA）。现有证据表明潜伏基因组是这些疱疹病毒甲基化的位点。我们得出结论，在嗜神经疱疹病毒中，感染性后代的正常潜伏前体没有甲基化，而CMV潜伏基因组中的立即早期基因座存在局部甲基化，并且这些嗜淋巴细胞疱疹病毒的潜伏基因组被广泛甲基化。
