A novel finding for enterovirus virulence from the capsid protein VP1 of EV71 circulating in mainland China
A novel finding for enterovirus virulence from the capsid protein VP1 of EV71 circulating in mainland China
复制标题
中国大陆流行的EV71衣壳蛋白VP1肠道病毒毒力的新发现
DOI：
10.1007/s11262-014-1035-2
复制
发表时间：
2014-04-01
期刊：
影响因子：
1.6
通讯作者：
He, Xiaohua
中科院分区：
文献类型：
--
作者：
Liu, Yongjuan;Fu, Chong;He, Xiaohua
肠道病毒 71 (EV71) 是一种嗜神经病毒，可导致幼儿出现各种临床表现，从无症状到致命。 EV71不同致病型的毒力差异显着。 EV71 的几个毒力决定因素已被预测。然而，这些报道的毒力决定子不能用于鉴定主要在中国流行的C4亚型EV71毒株。本研究对中国大陆37株EV71重症株（SC-EV71）和192株EV71轻症株（MC-EV71）的VP1序列进行分析，以确定EV71衣壳蛋白VP1的潜在毒力决定因素。尽管大多数 SC-EV71 毒株属于 C4a 亚基因型，但 C4a 中没有特定的遗传谱系与 EV71 毒力相关。有趣的是，通过比对 SC-EV71 和 MC-EV71 菌株的 VP1 序列，检测到 9 个位置（H22Q、P27S、N31S/D、E98K、E145G/Q、D164E、T240A/S、V249I 和 A289T）的氨基酸替换。此外，MC-EV71和SC-EV71株中保守或突变残基的构成比以及这些突变引起的VP1 3D结构的变化都证实了保守残基（22H、249V和289A）和突变残基（27S、31S/D、98K、145G/Q、164E和240A/S）可能是 EV71 VP1 的潜在毒力决定因素。此外，这些结果引发了这样的假设：VP1充当病毒颗粒稳定和细胞受体附着的三明治开关，并且该蛋白质的特定突变可以将轻度病例转化为重症病例。这些发现凸显了诊断和治疗干预的新机遇。
Enterovirus 71 (EV71) is a neurotropic virus that causes various clinical manifestations in young children, ranging from asymptomatic to fatal. Different pathotypes of EV71 notably differ in virulence. Several virulence determinants of EV71 have been predicted. However, these reported virulence determinants could not be used to identify the EV71 strains of subgenotype C4, which mainly circulate in China. In this study, VP1 sequences of 37 EV71 strains from severe cases (SC-EV71) and 192 EV71 strains from mild cases (MC-EV71) in mainland China were analyzed to determine the potential virulence determinants in the capsid protein VP1 of EV71. Although most SC-EV71 strains belonged to subgenotype C4a, no specific genetic lineages in C4a were correlated with EV71 virulence. Interestingly, amino acid substitutions at nine positions (H22Q, P27S, N31S/D, E98K, E145G/Q, D164E, T240A/S, V249I, and A289T) were detected by aligning the VP1 sequences of the SC-EV71 and MC-EV71 strains. Moreover, both the constituent ratios of the conservative or mutated residues in the MC-EV71 and SC-EV71 strains and the changes in the VP1 3D structure resulting from these mutations confirmed that the conservative residues (22H, 249V, and 289A) and the mutated residues (27S, 31S/D, 98K, 145G/Q, 164E, and 240A/S) might be potential virulence determinants in VP1 of EV71. Furthermore, these results led to the hypothesis that VP1 acts as a sandwich switch for viral particle stabilization and cellular receptors attachment, and specific mutations in this protein can convert mild cases into severe cases. These findings highlight new opportunities for diagnostic and therapeutic interventions.