The host’s immune status may affect virus evolution. Little is known about how developing fetal and placental immune milieus affect virus heterogeneity. This knowledge will help us better understand intra-host virus evolution and how new virus variants emerge. The goal of our study was to find out whether the isolated in utero environment—an environment with specialized placental immunity and developing fetal immunity—supports the emergence of RNA and DNA virus variants. We used well-established porcine models for isolated Zika virus (RNA virus) and porcine circovirus 2 (DNA virus) fetal infections. We found that the isolated in utero environment was conducive to the emergence of RNA and DNA virus variants. Next-generation sequencing of nearly whole virus genomes and validated bioinformatics pipelines identified both unique and convergent single nucleotide variations in virus genomes isolated from different fetuses. Zika virus and PCV2 in utero evolution also resulted in single nucleotide variations previously reported in the human and porcine field samples. These findings should encourage further studies on virus evolution in placenta and fetuses, to better understand how virus variants emerge and how in utero viral evolution affects congenital virus transmission and pathogenicity.

中文翻译：

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宫内环境中的分离物有利于 RNA 和 DNA 病毒变异体的出现

宿主的免疫状态可能会影响病毒的进化。关于发育中的胎儿和胎盘免疫环境如何影响病毒异质性知之甚少。这些知识将帮助我们更好地了解宿主内病毒的进化以及新病毒变种是如何出现的。我们研究的目的是查明分离的子宫内环境——具有专门的胎盘免疫和发育中的胎儿免疫的环境——是否支持 RNA 和 DNA 病毒变体的出现。我们使用成熟的猪模型进行分离的寨卡病毒（RNA 病毒）和猪圆环病毒 2（DNA 病毒）胎儿感染。我们发现，在子宫内环境中的分离有利于 RNA 和 DNA 病毒变体的出现。几乎整个病毒基因组的下一代测序和经过验证的生物信息学管道确定了从不同胎儿分离的病毒基因组中独特和收敛的单核苷酸变异。子宫内进化中的寨卡病毒和 PCV2 也导致先前在人类和猪场样本中报道的单核苷酸变异。这些发现应鼓励进一步研究胎盘和胎儿中的病毒进化，以更好地了解病毒变体如何出现以及子宫内病毒进化如何影响先天性病毒传播和致病性。