Exchanges of genomic domains between poliovirus and other cocirculating species C enteroviruses reveal a high degree of plasticity.

Exchanges of genomic domains between poliovirus and other cocirculating species C enteroviruses reveal a high degree of plasticity.
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脊髓灰质炎病毒和其他共循环物种之间基因组结构域C的交换表明,可塑性高度可塑性。

DOI:
10.1038/srep38831
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发表时间:
2016-12-13
期刊:
影响因子:
4.6
通讯作者:
Delpeyroux F
Delpeyroux F
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bessaud M;Joffret ML;Blondel B;Delpeyroux F

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口服脊髓灰质炎疫苗中包含的减毒沙宾毒株在遗传上不稳定,它们在免疫水平较低的人群中传播可能会导致致病性循环疫苗衍生脊髓灰质炎病毒(CVDPV)的出现。大多数cVDPV基因组的重组性质以及来自某些循环的C种非脊髓灰质炎肠道病毒(EV-Cs)的基因组序列的优先存在使人对EV-Cs之间的遗传交换的允许性和这种交换的表型影响提出了疑问。我们调查了功能限制是否限制了Sabin毒株与其他EV-Cs之间的遗传交流。我们绕过了自然重组事件,构建了29个基因组,其中包含Sabin 2衣壳编码序列和来自Sabin 2或非脊髓灰质炎EV-Cs的其他序列。大多数基因组是有功能的。所有重组病毒在体外复制相似,但重组调节斑块大小和温度敏感性。所有来自Sabin 2的5‘非编码区病毒在小鼠中都被减毒,而几乎所有非脊髓灰质炎5’非编码区的病毒都会引起疾病。这些数据突出了循环EV-Cs不同基因结构域之间功能兼容性的显著保守。这一方面只是在自然条件下产生重组cVDPV的条件之一,但它可能有助于产生具有不同表型特征(包括致病性)的可存活的跨型重组体。
The attenuated Sabin strains contained in the oral poliomyelitis vaccine are genetically unstable, and their circulation in poorly immunized populations can lead to the emergence of pathogenic circulating vaccine-derived polioviruses (cVDPVs). The recombinant nature of most cVDPV genomes and the preferential presence of genomic sequences from certain cocirculating non-polio enteroviruses of species C (EV-Cs) raise questions about the permissiveness of genetic exchanges between EV-Cs and the phenotypic impact of such exchanges. We investigated whether functional constraints limited genetic exchanges between Sabin strains and other EV-Cs. We bypassed the natural recombination events by constructing 29 genomes containing a Sabin 2 capsid-encoding sequence and other sequences from Sabin 2 or from non-polio EV-Cs. Most genomes were functional. All recombinant viruses replicated similarly in vitro, but recombination modulated plaque size and temperature sensitivity. All viruses with a 5′UTR from Sabin 2 were attenuated in mice, whereas almost all viruses with a non-polio 5′UTR caused disease. These data highlight the striking conservation of functional compatibility between different genetic domains of cocirculating EV-Cs. This aspect is only one of the requirements for the generation of recombinant cVDPVs in natural conditions, but it may facilitate the generation of viable intertypic recombinants with diverse phenotypic features, including pathogenicity.
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