An Effective Neutralizing Antibody Against Influenza Virus H1N1 from Human B Cells
An Effective Neutralizing Antibody Against Influenza Virus H1N1 from Human B Cells
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DOI：
10.1038/s41598-019-40937-4
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发表时间：
2019-03-14
影响因子：
4.6
通讯作者：
Wang, Andrew H-J
中科院分区：
文献类型：
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作者：
Lee, Cheng-Chung;Yang, Chih-Ya;Wang, Andrew H-J
流行性感冒是由流感病毒感染引起的急性呼吸道传染病。血凝素（HA）是流感病毒治疗和诊断检测的重要靶点。甲型流感病毒包括几种不同的HA亚型，具有不同的毒株，这些毒株不断变化。在这项研究中，我们通过EB病毒永生化B细胞为基础的技术，确定了一个完全人H1N1中和抗体（32 D 6）。32 D 6特异性中和2009年大流行后临床分离的H1N1毒株，但不中和早期毒株。通过对32 D 6-Fab/HA 1复合物结构的X射线晶体学分析鉴定了表位，其揭示了位于HA顶表面的独特环构象。主要区域由两个肽段（残基172-177和206-213）组成，其形成并列环构象。两个环之间的残基T262形成用于被32 D 6识别的构象表位。在HA和重链的界面处观察到三个水分子，它们可能构成32 D 6-HA缔合的稳定元素。此外，每个32 D 6-Fab可能能够阻断一个HA三聚体。本研究提供了关于32 D 6的菌株特异性的重要信息，用于病毒感染的治疗性治疗和检测。
Influenza is a contagious acute respiratory disease caused by the influenza virus infection. Hemagglutinin (HA) is an important target in the therapeutic treatment and diagnostic detection of the influenza virus. Influenza A virus encompasses several different HA subtypes with different strains, which are constantly changing. In this study, we identified a fully human H1N1 neutralizing antibody (32D6) via an Epstein-Barr virus-immortalized B cell-based technology. 32D6 specifically neutralizes the clinically isolated H1N1 strains after the 2009 pandemic but not the earlier strains. The epitope was identified through X-ray crystallographic analysis of the 32D6-Fab/HA1 complex structure, which revealed a unique loop conformation located on the top surface of HA. The major region is composed of two peptide segments (residues 172-177 and 206-213), which form an abreast loop conformation. The residue T262 between the two loops forms a conformational epitope for recognition by 32D6. Three water molecules were observed at the interface of HA and the heavy chain, and they may constitute a stabilizing element for the 32D6-HA association. In addition, each 32D6-Fab is likely capable of blocking one HA trimer. This study provides important information on the strain specificity of 32D6 for the therapeutic treatment and detection of viral infection.