Common and Diverse Features of Cocirculating Type 2 and 3 Recombinant Vaccine-Derived Polioviruses Isolated From Patients With Poliomyelitis and Healthy Children
Common and Diverse Features of Cocirculating Type 2 and 3 Recombinant Vaccine-Derived Polioviruses Isolated From Patients With Poliomyelitis and Healthy Children
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DOI：
10.1093/infdis/jis204
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发表时间：
2012-05-01
影响因子：
6.4
通讯作者：
Delpeyroux, Francis
中科院分区：
文献类型：
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作者：
Joffret, Marie-Line;Jegouic, Sophie;Delpeyroux, Francis
背景2005年，马达加斯加托利亚拉省报告了5例由2型或3型重组疫苗衍生脊髓灰质炎病毒（VDPVs）引起的脊髓灰质炎病例。方法。我们对从患者和12名健康儿童中分离的VDPV进行了基因组测序，并在脊髓灰质炎病毒受体转基因小鼠中表征了表型方面，包括致病性。我们鉴定了6个高度复杂的嵌合重组谱系，它们由来自不同疫苗脊髓灰质炎病毒和其他C类人类肠道病毒（HEV-C）的序列组成。大多数有一些共同的重组基因组特征，并包含与某些共循环科萨基A病毒分离株密切相关的核苷酸序列。然而，它们在重组特征或核苷酸取代和表型特征方面不同。所有VDPVs对小鼠均具有神经毒性。这项研究证实了2型和3型VDPV之间的遗传关系，表明两种类型都可能参与单一疾病的爆发。我们的结果强调了疫苗衍生脊髓灰质炎病毒在复杂的病毒生态系统中可能通过频繁的重组事件和突变而变得致病的各种方式。共循环HEV-C（包括脊髓灰质炎病毒）之间的型间重组似乎是横向遗传变异性的遗传可塑性的一种常见机制。
Background. Five cases of poliomyelitis due to type 2 or 3 recombinant vaccine-derived polioviruses (VDPVs) were reported in the Toliara province of Madagascar in 2005.Methods. We sequenced the genome of the VDPVs isolated from the patients and from 12 healthy children and characterized phenotypic aspects, including pathogenicity, in mice transgenic for the poliovirus receptor.Results. We identified 6 highly complex mosaic recombinant lineages composed of sequences derived from different vaccine polioviruses and other species C human enteroviruses (HEV-Cs). Most had some recombinant genome features in common and contained nucleotide sequences closely related to certain cocirculating coxsackie A virus isolates. However, they differed in terms of their recombinant characteristics or nucleotide substitutions and phenotypic features. All VDPVs were neurovirulent in mice.Conclusions. This study confirms the genetic relationship between type 2 and 3 VDPVs, indicating that both types can be involved in a single outbreak of disease. Our results highlight the various ways in which a vaccine-derived poliovirus may become pathogenic in complex viral ecosystems, through frequent recombination events and mutations. Intertypic recombination between cocirculating HEV-Cs (including polioviruses) appears to be a common mechanism of genetic plasticity underlying transverse genetic variability.