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Genetic characterization of enterovirus 71 isolated from patients with severe disease by comparative analysis of complete genomes

机译:通过完整基因组的比较分析从重症患者中分离出的肠道病毒71的遗传特征

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摘要

Enterovirus 71 (EV71) which causes mild illness in children is also associated with severe neurological complications. This study analyzed the complete genomes of EV71 strains derived from mild and severe diseases in order to determine whether the differences of EV71 genomes were responsible for different clinical presentations. Compared to complete genomes of EV71 strains derived from mild cases (less virulent strains), nucleotide differences in EV71 strains isolated from severe cases (more virulent strains) were observed primarily in the internal ribosomal entry site (IRES) of the 5′-untranslated region (UTR), which is vital for the cap-independent translation of viral proteins. In the protein-coding region, an E-Q substitution at amino acid position 145 of structural protein VP1 that occurred in more than one of more virulent strains was observed. This site is known to be related functionally to receptor binding and virulence in mice. Overall, strains (Group III) isolated from patients with fatal or severe sequelae outcomes had greater sequence substitutions in the 5′-UTR and/or protein-coding region and exhibited a relatively low-average homology to less virulent strains across the entire genome, indicating the possibility of significant genomic diversity in the most virulent EV71 strains. Further studies of EV71 pathogenesis should examine the significance of genomic diversity and the effects of multiple mutations in a viral population.
机译:引起儿童轻度疾病的肠病毒71(EV71)也与严重的神经系统并发症有关。这项研究分析了来自轻度和重度疾病的EV71菌株的完整基因组,以确定EV71基因组的差异是否导致了不同的临床表现。与源自轻度病例(低毒力菌株)的EV71菌株的完整基因组相比,从重症病例(高毒力菌株)分离的EV71菌株的核苷酸差异主要在5'非翻译区的内部核糖体进入位点(IRES)中观察到。 (UTR),这对于病毒蛋白的不依赖帽的翻译至关重要。在蛋白质编码区中,观察到在一种以上强毒株中发生的结构蛋白VP1氨基酸位置145处的E-Q取代。已知该位点在功能上与小鼠中的受体结合和毒力有关。总体而言,从具有致命或严重后遗症结局的患者中分离出的菌株(第III组)在5'-UTR和/或蛋白质编码区域具有更高的序列取代,并且与整个基因组中毒性较低的菌株相比,具有相对较低的平均同源性,表明在最强毒的EV71菌株中存在重要的基因组多样性。 EV71发病机理的进一步研究应检查基因组多样性的重要性以及病毒群体中多重突变的影响。

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