Genomic features of intertypic recombinant Sabin poliovirus strains excreted by primary vaccinees
Genomic features of intertypic recombinant Sabin poliovirus strains excreted by primary vaccinees
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DOI：
10.1128/jvi.75.13.5740-5751.2001
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发表时间：
2001-07-01
影响因子：
5.4
通讯作者：
Delpeyroux, F
中科院分区：
文献类型：
--
作者：
Cuervo, NS;Guillot, S;Delpeyroux, F
三价口服脊髓灰质炎疫苗（OPV）含有三种不同的脊髓灰质炎病毒血清型。因此，它的使用为肠细胞的混合感染创造了特别有利的条件，并且实际上在患有疫苗相关麻痹性脊髓灰质炎的患者中经常发现型间疫苗衍生的重组体（VdRec）。然而，在用OPV免疫接种后的健康疫苗接种者中尚未广泛搜索VdRec。为了确定VdRec的发生率及其在初次接种者中的排泄动力学，为了建立相应重组基因组的一般基因组特征，我们鉴定了OPV初次免疫后疫苗接种者分泌的脊髓灰质炎病毒分离株。通过多重限制性片段长度多态性分析鉴定重组菌株。还确定了重组基因组中连接位点的定位，疫苗接种后2至4天首次检测到疫苗分泌的VdRec。重组体的最高比率是在第14天。VdRec的频率强烈取决于所分析分离株的血清型（在最后排泄的1型、2型和3型分离株中分别有2%、53%和79%的重组菌株）。在重组基因组中，基因组片段的特定关联是优选的，并且在编码非结构蛋白的基因组区域中发现重组连接。扩增连接通常聚集在特定的亚基因组区域，这取决于分离株的血清型和/或重组体中基因组区段的关联。因此，VdRec经常由疫苗接种者分泌，并且脊髓灰质炎病毒复制机制要求或选择因子似乎在体内起作用以塑造重组基因组的特征。
The trivalent oral poliomyelitis vaccine (OPV) contains three different poliovirus serotypes. It use therefore creates particularly favorable conditions for mixed infection of gut cells, and indeed intertypic vaccine-derived recombinants (VdRec) have been frequently found in patients with vaccine-associated paralytic poliomyelitis, Nevertheless, there have not been extensive searches for VdRec in healthy vaccinees following immunization with OPV, To determine the incidence of VdRec and their excretion kinetics in primary vaccinees, and to establish the general genomic features of the corresponding recombinant genomes, we characterized poliovirus isolates excreted by vaccinees following primary immunization with OPV, Isolates were collected from 67 children 2 to 60 days following vaccination. Recombinant strains were identified by multiple restriction fragment length polymorphism assays. The localization of junction sites in recombinant genomes was also determined, VdRec excreted by vaccinees were first detected 2 to 4 days after vaccination. The highest rate of recombinants was on day 14, The frequency of VdRec depends strongly on the serotype of the analyzed isolates (2, 53, and 79% of recombinant strains in the last-excreted type 1, 2, and 3 isolates, respectively). Particular associations of genomic segments were preferred in the recombinant genomes, and recombination junctions were found in the genomic region encoding the nonstructural proteins. Recombination junctions generally clustered in particular subgenomic regions that were dependent on the serotype of the isolate and/or on the associations of genomic segments in recombinants, Thus, VdRec are frequently excreted by vaccinees, and the poliovirus replication machinery requirements or selection factors appear to act in vivo to shape the features of the recombinant genomes.