Antiviral defenses can sense viral RNAs and mediate their destruction. This presents a challenge for host cells since they must destroy viral RNAs while sparing the host mRNAs that encode antiviral effectors. Here, we show that highly upregulated interferon-stimulated genes (ISGs), which encode antiviral proteins, have distinctive nucleotide compositions. We propose that self-targeting by antiviral effectors has selected for ISG transcripts that occupy a less self-targeted sequence space. Following interferon (IFN) stimulation, the CpG-targeting antiviral effector zinc-finger antiviral protein (ZAP) reduces the mRNA abundance of multiple host transcripts, providing a mechanistic explanation for the repression of many (but not all) interferon-repressed genes (IRGs). Notably, IRGs tend to be relatively CpG rich. In contrast, highly upregulated ISGs tend to be strongly CpG suppressed. Thus, ZAP is an example of an effector that has not only selected compositional biases in viral genomes but also appears to have notably shaped the composition of host transcripts in the vertebrate interferome.

中文翻译：

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抗病毒状态塑造了脊椎动物干扰组的 CpG 组成，以避免自我靶向。

抗病毒防御可以感知病毒 RNA 并介导它们的破坏。这对宿主细胞提出了挑战，因为它们必须破坏病毒 RNA，同时保留编码抗病毒效应子的宿主 mRNA。在这里，我们表明编码抗病毒蛋白的高度上调的干扰素刺激基因 (ISG) 具有独特的核苷酸组成。我们建议抗病毒效应子的自我靶向已经选择了占据较少自我靶向序列空间的 ISG 转录本。在干扰素 (IFN) 刺激后，靶向 CpG 的抗病毒效应子锌指抗病毒蛋白 (ZAP) 降低了多个宿主转录物的 mRNA 丰度，为许多（但不是全部）干扰素抑制基因 (IRGs) 的抑制提供了机制解释）。值得注意的是，IRG 往往相对富含 CpG。相比之下，高度上调的 ISG 往往会受到强烈的 CpG 抑制。因此，ZAP 是一个效应器的例子，它不仅在病毒基因组中具有选择的组成偏差，而且似乎显着地塑造了脊椎动物干扰组中宿主转录物的组成。