Characterization of a cross-reactive monoclonal antibody against Norovirus genogroups I, II, III and V

Characterization of a cross-reactive monoclonal antibody against Norovirus genogroups I, II, III and V
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DOI:
10.1016/j.virusres.2010.04.005
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发表时间:
2010-08-01
期刊:
影响因子:
5
通讯作者:
Zhou, Zhichao
Zhou, Zhichao
中科院分区:
医学3区
文献类型:
--
作者:
Li, Xiao;Zhou, Rong;Zhou, Zhichao

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诺如病毒引起了世界范围内急性病毒性胃肠炎的大部分流行性暴发。在先前针对诺如病毒GII/4株的单克隆抗体的研究中,我们鉴定了被单克隆抗体N2 C3识别的连续表位(WIRNNF 60)-W-55。随后的研究发现,这种单克隆抗体可以识别几种不同的诺如病毒株,而不仅仅是GII/4。在本研究中,我们使用同源模建来证实N2 C3的表位暴露在GII/4衣壳蛋白的表面上。为了确定该表位在不同诺如病毒株中的保守性,构建了代表所有GI和GII毒株的37个诺如病毒株、2个牛诺如病毒(GIII)毒株和3个鼠诺如病毒(CV)毒株的氨基酸序列比对。使用诺如病毒中鉴定的15个突变的重组融合蛋白进行ELISA,其中12个被N2 C3识别。这12种肽代表了分布在整个基因组I、II、III和V中的29种诺如病毒株。据我们所知,这是首次鉴定能够检测人类和动物相关诺如病毒的交叉反应性单克隆抗体的研究。因此,单克隆抗体N2 C3可能是一个有用的工具,用于检测广泛的诺如病毒株。(C)2010 Elsevier B. V.保留所有权利。
Noroviruses cause the majority of epidemic outbreaks of acute viral gastroenteritis worldwide. In a previous study of monoclonal antibodies against Norovirus GII/4 strain, we identified a continuous epitope (WIRNNF60)-W-55 that was recognized by MAb N2C3. Subsequent studies found that this MAb could recognize several different strains of Noroviruses, not just GII/4. In the present study, we used homology modeling to confirm that the epitope of N2C3 was exposed on the surface of GII/4 capsid protein. To determine the conservation of this epitope in different strains of Noroviruses, an amino acid sequence alignment was constructed of 37 Norovirus strains representing all strains of GI and GII, 2 strains of Bovine Norovirus (GIII) and 3 strains of murine Norovirus (CV). ELISA was performed using recombinant fusion proteins of 15 mutations identified in Noroviruses and 12 were recognized by N2C3. These 12 peptides represented 29 Norovirus strains that were distributed throughout genogroups I, II, III and V. To our knowledge, this is the first study to identify a cross-reactive monoclonal antibody able to detect both human and animal-associated Noroviruses. Thus, MAb N2C3 is likely to be a useful tool for detecting a broad range of Norovirus strains. (C) 2010 Elsevier B.V. All rights reserved.