For viruses with segmented genomes, genetic diversity is generated by genetic drift, reassortment, and recombination. Recombination produces RNA populations distinct from full-length gene segments and can influence viral population dynamics, persistence, and host immune responses. Viruses in the Reoviridae family, including rotavirus and mammalian orthoreovirus (reovirus), have been reported to package segments containing rearrangements or internal deletions. Rotaviruses with RNA segments containing rearrangements have been isolated from immunocompromised and immunocompetent children and in vitro following serial passage at high multiplicity. Reoviruses that package small, defective RNA segments have established chronic infections in cells and in mice. However, the mechanism and extent of Reoviridae RNA recombination are undefined. Towards filling this gap in knowledge, we determined the titers and RNA segment profiles for reovirus and rotavirus following serial passage in cultured cells. The viruses exhibited occasional titer reductions characteristic of interference. Reovirus strains frequently accumulated segments that retained 5′ and 3′ terminal sequences and featured large internal deletions, while similar segments were rarely detected in rotavirus populations. Using next-generation RNA-sequencing to analyze RNA molecules packaged in purified reovirus particles, we identified distinct recombination sites within individual viral gene segments. Recombination junction sites were frequently associated with short regions of identical sequence. Taken together, these findings suggest that reovirus accumulates defective gene segments featuring internal deletions during passage and undergoes sequence-directed recombination at distinct sites.

中文翻译：

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呼肠孤病毒RNA重组是序列指导的，并在传代过程中产生内部缺失的有缺陷的基因组片段

对于具有分段基因组的病毒，遗传多样性是通过遗传漂移，重组和重组产生的。重组产生不同于全长基因区段的RNA种群，并且可以影响病毒种群动态，持久性和宿主免疫反应。据报道，呼肠孤病毒科中的病毒，包括轮状病毒和哺乳动物正咽病毒（呼肠孤病毒）包装了含有重排或内部缺失的片段。已从免疫功能低下和具有免疫能力的儿童中分离出具有重排RNA片段的轮状病毒，并在高通量连续传代后进行了体外分离。包装了小的，有缺陷的RNA片段的呼肠孤病毒已经在细胞和小鼠中建立了慢性感染。但是，呼肠孤病毒RNA重组的机制和程度尚不确定。为了填补这一知识空白，我们确定了在培养细胞中连续传代后呼肠孤病毒和轮状病毒的滴度和RNA片段谱。病毒偶尔表现出干扰的滴度降低。呼肠孤病毒株经常积累保留5'和3'末端序列并具有较大内部缺失的片段，而轮状病毒种群中很少检测到相似的片段。使用下一代RNA测序来分析包装在纯化呼肠孤病毒颗粒中的RNA分子，我们在单个病毒基因片段中鉴定出不同的重组位点。重组连接位点经常与相同序列的短区域相关。在一起