Does the Zinc Finger Antiviral Protein (ZAP) Shape the Evolution of Herpesvirus Genomes?
Does the Zinc Finger Antiviral Protein (ZAP) Shape the Evolution of Herpesvirus Genomes?
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DOI：
10.3390/v13091857
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发表时间：
2021-09-17
期刊：
影响因子：
--
通讯作者：
Grey F
中科院分区：
文献类型：
--
作者：
Lin YT;Chau LF;Coutts H;Mahmoudi M;Drampa V;Lee CH;Brown A;Hughes DJ;Grey F
病毒和宿主之间发生了一场进化的军备竞赛。宿主已经开发了一系列的抗病毒机制，旨在抑制病毒的复制和传播，降低它们的适应性，并最终将致病影响降至最低。反过来，病毒进化出复杂的应对措施，以调解对宿主防御机制的逃避。宿主防御的一个关键方面是区分自我和非我的能力。以前的研究已经证明，在RNA和小DNA病毒的编码区，CpG和uPA二核苷酸频率显著受到抑制。人为地增加这些二核苷酸的频率会导致病毒复制的显著减弱，这表明二核苷酸偏向可能有助于识别异体RNA。干扰素诱导基因锌指抗病毒蛋白(ZAP)是宿主因子，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。疱疹病毒是由阿尔法、贝塔和伽马三个亚家族组成的大型DNA病毒，在它们的基因组中显示出不同的CpG二核苷酸模式。ZAP最近被证明是对人类巨细胞病毒(HCMV)的宿主限制因子，HCMV是一种β-疱疹病毒，它通过抑制主要的即刻早期转录本IE1中的CpG水平来逃避ZAP的检测，IE1是病毒最早表达的基因之一。虽然抑制CpG二核苷酸可以逃避ZAP靶向，但引起基因组偏见的核苷酸组成的同义变化，如低GC含量，可能导致基因表达低效，特别是在未剪接的转录本中。为了保持基因组的紧凑，大多数疱疹病毒的转录本都是未拼接的。在这里，我们讨论ZAP逃避的冲突压力，通过使用非剪接转录本保持紧凑基因组的需要，以及保持有效的基因表达可能已经塑造了疱疹病毒基因组的进化，导致了特有的CpG二核苷酸模式。
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.
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DOI：
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发表时间：
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期刊：
Wiley interdisciplinary reviews. RNA
影响因子：
--
作者：
Gaunt ER;Digard P
通讯作者：
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影响因子：
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影响因子：
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