Dedepsidis Evaggelos, Karakasiliotis Ioannis, Paximadi Eleni, Kyriakopoulou Zaharoula, Komiotis Dimitrios, Markoulatos Panayotis
Department of Biochemistry & Biotechnology, School of Health Sciences, University of Thessaly, Ploutonos 26 & Aiolou, 41221 Larissa, Greece.
Virus Genes. 2006 Oct;33(2):183-91. doi: 10.1007/s11262-005-0055-3.
In the present study, a genomic analysis of full VP1 sequence region of 15 clinical re-isolates (14 healthy vaccinees and one bone marrow tumor patient) was conducted, aiming to the identification of mutations and to the assessment of their impact on virus fitness, providing also insights relevant with the natural evolution of Sabin strains. Clinical re-isolates were analyzed by RT-PCR, sequencing and computational analysis. Some re-isolates were characterized by an unusual mutational pattern in which non-synonymous mutations outnumbered the synonymous ones. Furthermore, the majority of amino-acid substitutions were located in the capsid exterior, specifically in N-Ags, near N-Ags and in the north rim of the canyon. Also mutations, which are well-known determinants of attenuation, were identified. The results of this study propose that some re-isolates are characterized by an evolutionary pattern in which non-synonymous mutations with a direct phenotypic impact on viral fitness are fixed in viral genomes, in spite of synonymous ones with no phenotypic impact on viral fitness. Results of the present retrospective characterization of Sabin clinical re-isolates, based on the full VP1 sequence, suggest that vaccine-derived viruses may make their way through narrow breaches and may evolve into transmissible pathogens even in adequately immunized populations. For this reason increased poliovirus laboratory surveillance should be permanent and full VP1 sequence analysis should be conducted even in isolates originating from healthy vaccinees.
在本研究中，对15株临床再分离株（14名健康疫苗接种者和1名骨髓肿瘤患者）的完整VP1序列区域进行了基因组分析，旨在识别突变并评估其对病毒适应性的影响，同时也为了解萨宾株的自然进化提供见解。通过逆转录聚合酶链反应（RT-PCR）、测序和计算分析对临床再分离株进行了分析。一些再分离株具有不寻常的突变模式，其中非同义突变的数量超过同义突变。此外，大多数氨基酸替换位于衣壳外部，特别是在N抗原、N抗原附近以及峡谷的北缘。还鉴定出了一些众所周知的减毒决定因素的突变。本研究结果表明，一些再分离株具有一种进化模式，即对病毒适应性有直接表型影响的非同义突变在病毒基因组中固定下来，尽管同义突变对病毒适应性没有表型影响。基于完整VP1序列对萨宾临床再分离株进行的本次回顾性特征分析结果表明，疫苗衍生病毒可能通过狭窄的缺口传播，甚至在免疫充分的人群中也可能进化为可传播的病原体。因此，应持续加强脊髓灰质炎病毒实验室监测，即使是来自健康疫苗接种者的分离株也应进行完整的VP1序列分析。
