Understanding how viruses with multi-segmented genomes incorporate one copy of each segment into their capsids remains an intriguing question. Here, we review our recent progress and describe the advancements made in understanding the genome packaging mechanism of a model nonenveloped virus, Bluetongue virus (BTV), with a 10-segment (S1–S10) double-strand RNA (dsRNA) genome. BTV (multiple serotypes), a member of the Orbivirus genus in the Reoviridae family, is a notable pathogen for livestock and is responsible for significant economic losses worldwide. This has enabled the creation of an extensive set of reagents and assays, including reverse genetics, cell-free RNA packaging, and bespoke bioinformatics approaches, which can be directed to address the packaging question. Our studies have shown that (i) UTRs enable the conformation of each segment necessary for the next level of RNA–RNA interaction; (ii) a specific order of intersegment interactions leads to a complex RNA network containing all the active components in sorting and packaging; (iii) networked segments are recruited into nascent assembling capsids; and (iv) select capsid proteins might be involved in the packaging process. The key features of genome packaging mechanisms for BTV and related dsRNA viruses are novel and open up new avenues of potential intervention.

中文翻译：

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RNA Origami：在 Orbivirus 组装和复制中包装分段基因组

了解具有多片段基因组的病毒如何将每个片段的一个副本整合到其衣壳中仍然是一个有趣的问题。在这里，我们回顾了我们最近的进展，并描述了在理解具有 10 段 (S1-S10) 双链 RNA (dsRNA) 基因组的模型无包膜病毒蓝舌病毒 (BTV) 的基因组包装机制方面取得的进展。BTV（多种血清型），呼肠孤病毒科环状病毒属的成员家畜，是一种重要的家畜病原体，在世界范围内造成重大经济损失。这使得创建大量试剂和分析成为可能，包括反向遗传学、无细胞 RNA 包装和定制的生物信息学方法，这些方法可以直接解决包装问题。我们的研究表明，（i）UTR 能够使每个片段的构象成为下一级 RNA-RNA 相互作用所必需的；(ii) 节间相互作用的特定顺序导致复杂的 RNA 网络包含分拣和包装中的所有活性成分；(iii) 网络部分被招募到新生的组装衣壳中；(iv) 选择的衣壳蛋白可能参与包装过程。