Sequence analysis of six enterovirus 71 strains with different virulences in humans
Sequence analysis of six enterovirus 71 strains with different virulences in humans
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DOI：
10.1016/j.virusres.2010.04.001
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发表时间：
2010-07-01
期刊：
影响因子：
5
通讯作者：
Zhu, Qing-yu
中科院分区：
文献类型：
--
作者：
Chang, Guo-hui;Lin, Lei;Zhu, Qing-yu
肠道病毒71型（EV 71）感染是手足口病（HFMD）的主要病因，并与严重的神经系统疾病相关，导致高死亡率。在这项研究中，从具有不同临床症状的患者中分离的6株EV 71菌株在EV 71感染的小鼠模型中进行测序和分析。在系统发育树中，基于完整的VP 1基因序列，所有6株菌株聚为C4基因型。序列分析表明，在5 '-非翻译区（5'-NTR）的内部核糖体进入位点（IRES）元件中存在核苷酸变化，以及在非结构蛋白中存在氨基酸差异。重要的是，我们鉴定了一个独特的氨基酸差异（瓦尔（1994）-Ile（1994）），该差异将强毒株安徽1号（Ah 1）、河南1号（Hn 1）和河南2号（Hn 2）与弱毒株重庆1号（Cq 1）、重庆2号（Cq 2）和重庆3号（Cq 3）区分开来。这种氨基酸差异位于病毒RNA依赖性RNA聚合酶3D（3D（Pol））的指状结构域中。此外，通过脑内或腹腔内途径将Ah 1、Hn 1、Hn 2、Cq 1、Cq 2和Cq 3分离株接种2日龄Balb/c小鼠。所有接种Ah 1、Hn 1和Hn 2分离株的小鼠均出现后肢麻痹，随后死亡。接种Cq 1、Cq 2或Cq 3分离株的小鼠在整个21天观察期内存活。这些结果显示，与人类不同严重程度疾病相关的EV 71临床分离株具有特征性序列差异，并在接种到小鼠中时引起不同的死亡率。这些数据也提供了一个合理的基础上，研究分子决定因素的EV 71发病机制，使用反向遗传学的方法。(C)2010 Elsevier B. V.保留所有权利。
Enterovirus 71 (EV71) infection is the main cause of hand, foot and mouth disease (HFMD) and has been associated with severe neurological diseases resulting in high mortalities. In this study, six EV71 strains isolated from patients with different clinical symptoms were sequenced and analyzed in a mouse model of EV71 infection. In a phylogenetic tree, based on the complete VP1 gene sequence, all six strains grouped into the C4 genotype. The sequence analysis revealed that there are nucleotide changes clustered in the internal ribosome entry site (IRES) element of the 5'-nontranslated region (5'-NTR), as well as amino acid differences clustered in the non-structural proteins. Importantly, we identified a unique amino acid difference (Val(1994)-Ile(1994)) that distinguished the more virulent strains, Anhui1 (Ah1), Henan1 (Hn1) and Henan2 (Hn2) from the less virulent strains, Chongqing1 (Cq1), Chongqing2 (Cq2) and Chongqing3 (Cq3). This amino acid difference is located in the finger domain of the viral RNA-dependent RNA polymerase 3D (3D(Pol)). Furthermore, two-day-old Balb/c mice were inoculated with the Ah1, Hn1, Hn2, Cq1, Cq2 and Cq3 isolates by the intracerebral or intraperitoneal routes. All of the mice inoculated with Ah1, Hn1 and Hn2 isolates developed hind-leg paralysis and subsequently died. Mice inoculated with the Cq1, Cq2 or Cq3 isolates survived throughout the 21-day observation period. These results show that clinical isolates of EV71 associated with disease of different severity in humans have characteristic sequence differences and cause different mortality rates when inoculated into mice. These data also provide a rational basis to investigate the molecular determinants of EV71 pathogenesis using a reverse genetic approach. (C) 2010 Elsevier B.V. All rights reserved.