Identification of a blockade epitope of human norovirus GII.17.

Identification of a blockade epitope of human norovirus GII.17.
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人诺如病毒 GII.17 阻断表位的鉴定

DOI:
10.1080/22221751.2021.1925162
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发表时间:
2021-12
影响因子:
13.2
通讯作者:
Huang Z
Huang Z
中科院分区:
医学2区
文献类型:
--
作者:
Yi Y;Wang X;Wang S;Xiong P;Liu Q;Zhang C;Yin F;Huang Z

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人类诺如病毒是全球急性病毒性胃肠炎的主要病原体。在2014-2015年冬季,基因型GII.17簇IIIb毒株成为亚洲诺如病毒感染的主要原因,后来传播到世界其他地区。据推测,阻断表位的突变可能导致病毒逃避群体免疫,导致GII.17簇IIIb变体的出现。在这里,我们通过基于单克隆抗体(mAb)的表位作图确定了GII.17簇IIIb特异性阻断表位。从用GII.17簇IIIb毒株的病毒样颗粒(VLP)免疫的小鼠产生4种mAb(命名为M1至M4)。其中,M1和M3与IIIb族VLP特异性反应,但不与来自II族或IIIa族的VLP反应。此外,M1和M3剂量依赖性地阻断簇IIIb VLP与其配体组织血型抗原(HBGAs)的结合。表位作图显示,M1和M3识别由衣壳蛋白VP 1中的残基293-296和299组成的相同的高度暴露的表位。序列比对显示,M1/M3表位序列在不同的GII.17簇之间高度可变,而对于簇IIIIb菌株是相同的。这些数据定义了GII.17诺如病毒的显性阻断表位,并提供了阻断表位进化有助于GII.17簇IIIb毒株出现的证据。
Human noroviruses are the dominant causative agent of acute viral gastroenteritis worldwide. During the winter of 2014–2015, genotype GII.17 cluster IIIb strains emerged as the leading cause of norovirus infection in Asia and later spread to other parts of the world. It is speculated that mutation at blockade epitopes may have resulted in virus escape from herd immunity, leading to the emergence of GII.17 cluster IIIb variants. Here, we identify a GII.17 cluster IIIb-specific blockade epitope by monoclonal antibody (mAb)-based epitope mapping. Four mAbs (designated as M1 to M4) were generated from mice immunized with virus-like particle (VLP) of a GII.17 cluster IIIb strain. Among them, M1 and M3 reacted specifically with the cluster IIIb VLP but not with the VLPs from clusters II or IIIa. Moreover, M1 and M3 dose-dependently blocked cluster IIIb VLP binding with its ligand, histo-blood group antigens (HBGAs). Epitope mapping revealed that M1 and M3 recognized the same highly exposed epitope consisting of residues 293–296 and 299 in the capsid protein VP1. Sequence alignment showed that the M1/M3 epitope sequence is highly variable among different GII.17 clusters whereas it is identical for cluster IIIIb strains. These data define a dominant blockade epitope of GII.17 norovirus and provide evidence that blockade epitope evolution contributes to the emergence of GII.17 cluster IIIb strains.
DOI: 10.2807/1560-7917.es2015.20.24.21157
发表时间: 2015-06-18
期刊: EUROSURVEILLANCE
影响因子: 19
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期刊: EUROSURVEILLANCE
影响因子: 19
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