Genomic Diversity and Evolution of Quasispecies in Newcastle Disease Virus Infections.

Genomic Diversity and Evolution of Quasispecies in Newcastle Disease Virus Infections.
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DOI:
10.3390/v12111305
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发表时间:
2020-11-14
期刊:
Viruses
影响因子:
--
通讯作者:
Ferretti L
Ferretti L
中科院分区:
其他
文献类型:
--
作者:
Jadhav A;Zhao L;Liu W;Ding C;Nair V;Ramos-Onsins SE;Ferretti L

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众所周知,由于RNA聚合酶的易错性,纽卡斯尔病病毒(NDV)感染具有准种。已知病毒融合切割位点中的准种变体显著改变其毒力。然而,对NDV病毒群的基因组多样性和选择模式知之甚少。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NDV群内的基因组多样性模式和选择特征。来自体外样品的病毒变异体主要位于非编码区和3′和5′非翻译区(3′ UTR或5′ UTR),而体内样品含有数量级更多的变异体。我们发现NDV基因型之间的基因组差异和多样性的不同模式,以及在体外和体内感染的相同菌株之间的宿主内变异体的基因组分布的差异。该频谱显示了对基质蛋白(M)编码基因的体内宿主内纯化选择以及对核衣壳(NP)和血凝素-神经氨酸酶(HN)的阳性或多样化选择的清晰特征。宿主内多态性和系统发育分化之间的比较揭示了NDV基因组在宿主间和宿主内水平上的选择压力的复杂模式。M序列在宿主间和宿主内均受到强烈的限制,融合蛋白(F)编码基因在宿主内受到正选择,NP和HN表现出相反的模式:HN RNA序列在宿主间受到正选择,而其蛋白质序列在宿主内受到正选择,NP在RNA水平上受到宿主内正选择,在蛋白质水平上受到宿主内负选择。
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.
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