Immunodominant IgM and IgG Epitopes Recognized by Antibodies Induced in Enterovirus A71-Associated Hand, Foot and Mouth Disease Patients.
Immunodominant IgM and IgG Epitopes Recognized by Antibodies Induced in Enterovirus A71-Associated Hand, Foot and Mouth Disease Patients.
复制标题
DOI：
10.1371/journal.pone.0165659
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Chan YF
中科院分区：
文献类型：
--
作者：
Aw-Yong KL;Sam IC;Koh MT;Chan YF
肠道病毒A71（EV-A71）是手足口病（HFMD）的主要病原体之一。与其他引起手足口病的肠道病毒不同，EV-A71 更常与严重的神经系统并发症和死亡相关。迄今为止，尚无有效的许可抗病毒药物可用于对抗 EV-A71 感染。人们对病毒非结构蛋白在人类中的免疫原性知之甚少。之前的研究主要集中在使用免疫动物抗血清来表征 EV-A71 结构蛋白的表位。在这项研究中，我们表征了针对 EV-A71 结构和非结构蛋白的人类抗体反应。每种病毒蛋白都在细菌或哺乳动物系统中克隆和表达，并通过蛋白质印迹法用抗血清进行测试。结果显示，所有结构蛋白 (VP1-4) 和非结构蛋白 2A、3C 和 3D 都是 EV-A71 IgM 的目标，而 EV-A71 IgG 识别所有结构和非结构蛋白。合成了 63 种预计在计算机中具有免疫原性的合成肽，并用于表征 EV-A71 线性 B 细胞表位。我们总共鉴定了 22 个 IgM 和 4 个 IgG 优势表位。合成肽 PEP27，对应于 VP1 的残基 142-156，被鉴定为 EV-A71 IgM 特异性免疫显性表位。 PEP23 映射到 VP1 41-55，被认为是 EV-A71 IgG 交叉反应免疫显性表位。结构蛋白 VP1 是抗 EV-A71 IgM 和 IgG 抗体靶向的主要免疫显性位点，但也检测到针对非结构蛋白的表位。这些数据提供了对 EV-A71 感染免疫反应的新认识，有利于诊断工具、潜在治疗方法和候选亚单位疫苗的开发。
Enterovirus A71 (EV-A71) is one of the main causative agents of hand, foot and mouth disease (HFMD). Unlike other enteroviruses that cause HFMD, EV-A71 is more frequently associated with severe neurological complications and fatality. To date, no effective licensed antivirals are available to combat EV-A71 infection. Little is known about the immunogenicity of viral non-structural proteins in humans. Previous studies have mainly focused on characterization of epitopes of EV-A71 structural proteins by using immunized animal antisera. In this study, we have characterized human antibody responses against the structural and non-structural proteins of EV-A71. Each viral protein was cloned and expressed in either bacterial or mammalian systems, and tested with antisera by western blot. Results revealed that all structural proteins (VP1-4), and non-structural proteins 2A, 3C and 3D were targets of EV-A71 IgM, whereas EV-A71 IgG recognized all the structural and non-structural proteins. Sixty three synthetic peptides predicted to be immunogenic in silico were synthesized and used for the characterization of EV-A71 linear B-cell epitopes. In total, we identified 22 IgM and four IgG dominant epitopes. Synthetic peptide PEP27, corresponding to residues 142–156 of VP1, was identified as the EV-A71 IgM-specific immunodominant epitope. PEP23, mapped to VP1 41–55, was recognized as the EV-A71 IgG cross-reactive immunodominant epitope. The structural protein VP1 is the major immunodominant site targeted by anti-EV-A71 IgM and IgG antibodies, but epitopes against non-structural proteins were also detected. These data provide new understanding of the immune response to EV-A71 infection, which benefits the development of diagnostic tools, potential therapeutics and subunit vaccine candidates.
登录
查看更多内容
影响因子：
2.6
作者：
Bronsvoort, Barend M deC;Toft, Nils;Morgan, Kenton L
通讯作者：
Morgan, Kenton L
抗 71 型肠道病毒的人 IgG 亚类：中和作用与抗体依赖性感染增强作用
影响因子：
3.7
作者：
Cao RY;Dong DY;Liu RJ;Han JF;Wang GC;Zhao H;Li XF;Deng YQ;Zhu SY;Wang XY;Lin F;Zhang FJ;Chen W;Qin ED;Qin CF
通讯作者：
Qin CF
影响因子：
5
作者：
Guang, Damian;Foo, Wei;Poh, Chit Laa
通讯作者：
Poh, Chit Laa
影响因子：
5
作者：
AbuBakar, S;Chee, HY;Lam, SK
通讯作者：
Lam, SK
影响因子：
4.8
作者：
Gao F;Wang YP;Mao QY;Yao X;Liu S;Li FX;Zhu FC;Yang JY;Liang ZL;Lu FM;Wang JZ
通讯作者：
Wang JZ