An evolutionary arms race occurs between viruses and hosts. Hosts have developed an array of antiviral mechanisms aimed at inhibiting replication and spread of viruses, reducing their fitness, and ultimately minimising pathogenic effects. In turn, viruses have evolved sophisticated counter-measures that mediate evasion of host defence mechanisms. A key aspect of host defences is the ability to differentiate between self and non-self. Previous studies have demonstrated significant suppression of CpG and UpA dinucleotide frequencies in the coding regions of RNA and small DNA viruses. Artificially increasing these dinucleotide frequencies results in a substantial attenuation of virus replication, suggesting dinucleotide bias could facilitate recognition of non-self RNA. The interferon-inducible gene, zinc finger antiviral protein (ZAP) is the host factor responsible for sensing CpG dinucleotides in viral RNA and restricting RNA viruses through direct binding and degradation of the target RNA. Herpesviruses are large DNA viruses that comprise three subfamilies, alpha, beta and gamma, which display divergent CpG dinucleotide patterns within their genomes. ZAP has recently been shown to act as a host restriction factor against human cytomegalovirus (HCMV), a beta-herpesvirus, which in turn evades ZAP detection by suppressing CpG levels in the major immediate-early transcript IE1, one of the first genes expressed by the virus. While suppression of CpG dinucleotides allows evasion of ZAP targeting, synonymous changes in nucleotide composition that cause genome biases, such as low GC content, can cause inefficient gene expression, especially in unspliced transcripts. To maintain compact genomes, the majority of herpesvirus transcripts are unspliced. Here we discuss how the conflicting pressures of ZAP evasion, the need to maintain compact genomes through the use of unspliced transcripts and maintaining efficient gene expression may have shaped the evolution of herpesvirus genomes, leading to characteristic CpG dinucleotide patterns.

中文翻译：

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锌指抗病毒蛋白 (ZAP) 是否影响疱疹病毒基因组的进化？

病毒和宿主之间发生了进化军备竞赛。宿主已经开发出一系列抗病毒机制，旨在抑制病毒的复制和传播，降低它们的适应性，并最终最大限度地减少致病作用。反过来，病毒已经进化出复杂的对抗措施，可以介导逃避宿主防御机制。宿主防御的一个关键方面是区分自我和非自我的能力。以前的研究表明，RNA 和小 DNA 病毒编码区的 CpG 和 UpA 二核苷酸频率显着抑制。人为地增加这些二核苷酸频率会导致病毒复制的显着减弱，这表明二核苷酸偏差可以促进对非自身 RNA 的识别。干扰素诱导基因，锌指抗病毒蛋白 (ZAP) 是负责感知病毒 RNA 中的 CpG 二核苷酸并通过直接结合和降解靶 RNA 来限制 RNA 病毒的宿主因子。疱疹病毒是大型 DNA 病毒，包括三个亚科，α、β 和 γ，它们在其基因组中显示出不同的 CpG 二核苷酸模式。ZAP 最近已被证明可作为宿主限制因子来对抗人类巨细胞病毒 (HCMV)，这是一种 β-疱疹病毒，它反过来通过抑制主要立即早期转录物 IE1 中的 CpG 水平来逃避 ZAP 检测，IE1 是最早表达的基因之一。病毒。虽然抑制 CpG 二核苷酸可以逃避 ZAP 靶向，但导致基因组偏差的核苷酸组成的同义变化，例如低 GC 含量，可能导致基因表达效率低下，尤其是在未拼接的转录本中。为了保持紧凑的基因组，大多数疱疹病毒转录本是未剪接的。在这里，我们讨论了 ZAP 逃避的相互冲突的压力、通过使用未剪接的转录物来维持紧凑基因组的需要以及维持有效的基因表达可能如何塑造了疱疹病毒基因组的进化，从而导致了特征性的 CpG 二核苷酸模式。