Newcastle disease virus (NDV) infections are well known to harbour quasispecies, due to the error-prone nature of the RNA polymerase. Quasispecies variants in the fusion cleavage site of the virus are known to significantly change its virulence. However, little is known about the genomic patterns of diversity and selection in NDV viral swarms. We analyse deep sequencing data from in vitro and in vivo NDV infections to uncover the genomic patterns of diversity and the signatures of selection within NDV swarms. Variants in viruses from in vitro samples are mostly localised in non-coding regions and 3′ and 5′ untranslated regions (3′UTRs or 5′UTRs), while in vivo samples contain an order of magnitude more variants. We find different patterns of genomic divergence and diversity among NDV genotypes, as well as differences in the genomic distribution of intra-host variants among in vitro and in vivo infections of the same strain. The frequency spectrum shows clear signatures of intra-host purifying selection in vivo on the matrix protein (M) coding gene and positive or diversifying selection on nucleocapsid (NP) and haemagglutinin-neuraminidase (HN). The comparison between within-host polymorphisms and phylogenetic divergence reveals complex patterns of selective pressure on the NDV genome at between- and within-host level. The M sequence is strongly constrained both between and within hosts, fusion protein (F) coding gene is under intra-host positive selection, and NP and HN show contrasting patterns: HN RNA sequence is positively selected between hosts while its protein sequence is positively selected within hosts, and NP is under intra-host positive selection at the RNA level and negative selection at the protein level.

中文翻译：

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新城疫病毒感染的基因组多样性和拟种进化

由于RNA聚合酶易出错的性质，众所周知，新城疫病毒（NDV）感染具有准种。已知病毒融合切割位点的准种变体会显着改变其毒力。然而，关于NDV病毒群的多样性和选择的基因组模式知之甚少。我们分析了来自体外和体内NDV感染的深度测序数据，以揭示多样性的基因组模式和NDV群内选择的标志。来自体外样品的病毒变异体大多位于非编码区以及3'和5'非翻译区（3'UTR或5'UTR），而体内样品则包含一个数量级以上的变异体。我们发现NDV基因型之间基因组差异和多样性的不同模式，以及同一菌株的体外和体内感染之间宿主内变体的基因组分布差异。频谱显示了在基质蛋白（M）编码基因上的体内宿主纯化选择的清晰特征，以及在核衣壳（NP）和血凝素神经氨酸酶（HN）上的阳性或多样化选择。寄主内部多态性与系统发育差异之间的比较揭示了寄主之间和寄主内部水平上NDV基因组选择性压力的复杂模式。M序列受到宿主之间和宿主之间的强烈限制，融合蛋白（F）编码基因处于宿主内阳性选择之下，而NP和HN显示出相反的模式：HN RNA序列在宿主之间阳性选择，而其蛋白质序列阳性选择在主机内