An attenuated strain of enterovirus 71 belonging to genotype A showed a broad spectrum of antigenicity with attenuated neurovirulence in cynomolgus monkeys
An attenuated strain of enterovirus 71 belonging to genotype A showed a broad spectrum of antigenicity with attenuated neurovirulence in cynomolgus monkeys
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DOI：
10.1128/jvi.02856-06
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发表时间：
2007-09-01
影响因子：
5.4
通讯作者：
Shimizu, Hiroyuki
中科院分区：
文献类型：
--
作者：
Arita, Minetaro;Nagata, Noriyo;Shimizu, Hiroyuki
肠病毒71型（EV71）是手足口病的病原体，有时也与严重的神经系统疾病有关。在本研究中，我们在猴感染模型中鉴定了一株基因型为A的EV71减毒株[EV71(S1-3')]的抗原性和组织特异性。3只食蟹猴接种了EV71（S1-3′），在接种EV71（S1-3′）后第45天，用亲本毒株EV71（BrCr-TR）静脉致死性攻毒。接种了EV71（S1-3′）的猴子表现出轻微的神经症状（震颤），但在毒力EV71（BrCr-TR）的致命攻击中存活下来，没有症状加重。免疫后的猴血清对不同基因型EV71病毒表现出广泛的中和活性，包括基因型a、B1、B4、C2和C4。检测的菌株血清对基因型A的中和活性最高，对基因型C2的中和活性最低。血清中和活性降低的顺序为：A > B1 > C4 > B4 > C2。为了检验EV71（S1-3′）的组织特异性，对2只猴子静脉注射EV71（S1-3′），观察病毒在中枢神经系统和神经外组织中的分布。在中枢神经系统，EV71（S1-3′）仅从脊髓分离。这些结果表明，EV71（S1-3′）作为一种有效的抗原，尽管该减毒株经静脉注射后仍具有嗜神经性。
Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and is also sometimes associated with serious neurological disorders. In this study, we characterized the antigenicity and tissue specificity of an attenuated strain of EV71 [EV71(S1-3')], which belongs to genotype A, in a monkey infection model. Three cynomolgus monkeys were inoculated with EV71 (S1-3'), followed by lethal challenge with the parental virulent strain EV71(BrCr-TR) via an intravenous route on day 45 postinoculation of EV71(S1-3'). Monkeys inoculated with EV71(S1-3') showed a mild neurological symptom (tremor) but survived lethal challenge by virulent EV71(BrCr-TR) without exacerbation of the symptom. The immunized monkey sera showed a broad spectrum of neutralizing activity against different genotypes of EV71, including genotypes A, B1, B4, C2, and C4. For the strains examined, the sera showed the highest neutralization activity against the homotype (genotype A) and the lowest neutralization activity against genotype C2. The order of decreasing neutralization activity of sera was as follows: A > B1 > C4 > B4 > C2. To examine the tissue specificity of EV71(S1-3'), two monkeys were intravenously inoculated with EV71(S1-3' followed by examination of virus distribution in the central nervous system (CNS) and extraneural tissues. In the CNS, EV71(S1-3') was isolated only from the spinal cord. These results indicate that EV71(S1-3') acts as an effective antigen, although this attenuated strain was still neurotropic when inoculated via the intravenous route.