The presence of CpG and UpA dinucleotides is restricted in the genomes of animal RNA viruses to avoid specific host defenses. We wondered whether a similar phenomenon exists in nonanimal RNA viruses. Here, we show that these two dinucleotides, especially UpA, are underrepresented in the family Potyviridae, the most important group of plant RNA viruses. Using plum pox virus (PPV; Potyviridae family) as a model, we show that an increase in UpA frequency strongly diminishes virus accumulation. Remarkably, unlike previous observations in animal viruses, PPV variants harboring CpG-rich fragments display just faint (or no) attenuation. The anticorrelation between UpA frequency and viral fitness additionally demonstrates the relevance of this particular dinucleotide: UpA-high mutants are attenuated in a dose-dependent manner, whereas a UpA-low variant displays better fitness than its parental control. Using high-throughput sequencing, we also show that UpA-rich PPV variants are genetically stable, without apparent changes in sequence that revert and/or compensate for the dinucleotide modification despite its attenuation. In addition, we also demonstrate here that the PPV restriction of UpA-rich variants works independently of the classical RNA silencing pathway. Finally, we show that the anticorrelation between UpA frequency and RNA accumulation applies to mRNA-like fragments produced by the host RNA polymerase II. Together, our results inform us about a dinucleotide-based system in plant cells that controls diverse RNAs, including RNA viruses.IMPORTANCE Dinucleotides (combinations of two consecutive nucleotides) are not randomly present in RNA viruses; in fact, the presence of CpG and UpA is significantly repressed in their genomes. Although the meaning of this phenomenon remains obscure, recent studies with animal-infecting viruses have revealed that their low CpG/UpA frequency prevents virus restriction via a host antiviral system that recognizes, and promotes the degradation of, CpG/UpA-rich RNAs. Whether similar systems act in organisms from other life kingdoms has been unknown. To fill this gap in our knowledge, we built several synthetic variants of a plant RNA virus with deoptimized dinucleotide frequencies and analyzed their viral fitness and genome adaptation. In brief, our results inform us for the first time about an effective dinucleotide-based system that acts in plants against viruses. Remarkably, this viral restriction in plants is reminiscent of, but not identical to, the equivalent antiviral response in animals.

中文翻译：

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植物病毒基因组受到影响病毒感染的特定二核苷酸限制的影响。

CpG和UpA二核苷酸的存在被限制在动物RNA病毒的基因组中，以避免特定的宿主防御。我们想知道非动物RNA病毒中是否存在类似现象。在这里，我们显示这两个二核苷酸，特别是UpA，在植物RNA病毒最重要的一类Potyviridae中的代表性不足。使用李子痘病毒（PPV； Potyviridae家族）作为模型，我们显示UpA频率的增加会大大减少病毒的积累。值得注意的是，与先前在动物病毒中的观察结果不同，带有富含CpG片段的PPV变体仅表现出微弱的衰减（或没有衰减）。UpA频率与病毒适应性之间的反相关性进一步证明了这种特定二核苷酸的相关性：UpA高突变体以剂量依赖性方式减弱，而UpA-low变体的适应性要比其父母对照更好。使用高通量测序，我们还显示，富含UpA的PPV变体在遗传上是稳定的，尽管在序列上没有明显的变化，尽管其衰减了，但该序列不会还原和/或补偿二核苷酸修饰。此外，我们在此处还证明了UpA丰富变体的PPV限制独立于经典RNA沉默途径而起作用。最后，我们表明UpA频率和RNA积累之间的反相关适用于宿主RNA聚合酶II产生的mRNA样片段。总之，我们的结果告诉我们有关植物细胞中基于双核苷酸的系统，该系统可控制多种RNA，包括RNA病毒。重要信息RNA病毒中并非随机存在双核苷酸（两个连续核苷酸的组合）。事实上，CpG和UpA的存在在其基因组中被显着抑制。尽管这种现象的含义仍然不清楚，但是最近有关动物感染病毒的研究表明，其低CpG / UpA频率可通过识别并促进富含CpG / UpA的RNA的宿主抗病毒系统阻止病毒的限制。尚不清楚类似系统是否在其他生命王国的生物中起作用。为了填补我们的知识空白，我们构建了几种植物RNA病毒的合成变体，其双核苷酸频率未优化，并分析了它们的病毒适应性和基因组适应性。简而言之，我们的结果首次为我们提供了一种有效的基于二核苷酸的系统，该系统可在植物中发挥抗病毒作用。值得注意的是，这种病毒对植物的限制使人想起但并不等同于