Atomic structures of Coxsackievirus A6 and its complex with a neutralizing antibody.

Atomic structures of Coxsackievirus A6 and its complex with a neutralizing antibody.
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柯萨奇病毒 A6 及其与中和抗体复合物的原子结构

DOI:
10.1038/s41467-017-00477-9
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发表时间:
2017-09-11
影响因子:
16.6
通讯作者:
Xia N
Xia N
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Xu L;Zheng Q;Li S;He M;Wu Y;Li Y;Zhu R;Yu H;Hong Q;Jiang J;Li Z;Li S;Zhao H;Yang L;Hou W;Wang W;Ye X;Zhang J;Baker TS;Cheng T;Zhou ZH;Yan X;Xia N

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柯萨奇病毒A6 (CVA6)最近已成为全球儿童手足口病的主要病因,但目前尚无针对CVA6感染的疫苗。在这里,我们展示了两种稳定的CVA6颗粒-原衣壳和a -颗粒的分离,它们具有优异的生化稳定性和天然抗原性,可作为候选疫苗。尽管存在(在a粒子中)或不存在(在原衣壳中)衣壳- rna相互作用,但两种CVA6粒子具有本质上相同的原子衣壳结构,类似于其他肠病毒的剥膜中间体。我们的近原子分辨率结构的CVA6 -a粒子与中和抗体络合,将免疫优势中和表位映射到VP1的表面环。基于结构引导的细胞抑制研究进一步证明,这些环可以作为设计抗cva6疫苗的优秀靶点。
Coxsackievirus A6 (CVA6) has recently emerged as a major cause of hand, foot and mouth disease in children worldwide but no vaccine is available against CVA6 infections. Here, we demonstrate the isolation of two forms of stable CVA6 particles-procapsid and A-particle-with excellent biochemical stability and natural antigenicity to serve as vaccine candidates. Despite the presence (in A-particle) or absence (in procapsid) of capsid-RNA interactions, the two CVA6 particles have essentially identical atomic capsid structures resembling the uncoating intermediates of other enteroviruses. Our near-atomic resolution structure of CVA6 A-particle complexed with a neutralizing antibody maps an immune-dominant neutralizing epitope to the surface loops of VP1. The structure-guided cell-based inhibition studies further demonstrate that these loops could serve as excellent targets for designing anti-CVA6 vaccines.
DOI: 10.1126/sciadv.1501929
发表时间: 2016-08
期刊: Science advances
影响因子: 13.6
作者:
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通讯作者: Hafenstein S
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发表时间: 2013-06
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影响因子: 48
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发表时间: 2010-02
期刊: Acta crystallographica. Section D, Biological crystallography
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发表时间: 2015-01-02
期刊: Science (New York, N.Y.)
影响因子: --
作者:
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通讯作者: Rossmann MG