Department of Biological Sciences, Purdue University, West Lafayette, Indiana, USA.
Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
J Virol. 2019 Apr 17;93(9). doi: 10.1128/JVI.01732-18. Print 2019 May 1.
Parvovirus B19, one of the most common human pathogens, is a small DNA virus that belongs to the As a result of previous infections, antibodies to B19 are present in most adults. B19 has a strong tropism to erythroid progenitor cells and is able to cause a series of medical conditions, including fifth disease, arthritis, myocarditis, hydrops fetalis, and aplastic crisis. No approved vaccine is currently available for B19, and there is a lack of structural characterization of any B19 epitopes. Here we present the first cryo-electron microscopy (cryo-EM) structure of a B19 virus-like particle (VLP) complexed with the antigen-binding fragment (Fab) of a human neutralizing antibody, 860-55D. A model was built into the 3.2-Å-resolution map, and the antigenic residues on the surface of the B19 capsid were identified. Antibody 860-55D bridges the capsid of B19 by binding to a quaternary structure epitope formed by residues from three neighboring VP2 capsid proteins. Parvovirus B19 is a common human pathogen and a particular threat to children, pregnant women, and patients with sickle cell disease or AIDS. Currently, neutralizing antibody is the most efficient treatment for acute B19 infections. Research on the antigenic properties of B19 will guide the usage of these antibodies and facilitate vaccine development. We have determined and report here the high-resolution structure of B19 virus-like particles (VLPs) complexed with the Fab of a human neutralizing antibody. The structure shows a quaternary structure epitope formed by three VP2 proteins and provides details on host recognition of human B19 virus.
细小病毒 B19 是最常见的人类病原体之一，属于细小病毒科。由于先前的感染，大多数成年人都存在针对 B19 的抗体。B19 对红系祖细胞具有强烈的亲嗜性，能够引起一系列医学病症，包括第五病、关节炎、心肌炎、胎儿水肿和再生障碍性危象。目前尚无针对 B19 的批准疫苗，并且对任何 B19 表位的结构特征描述都很缺乏。在这里，我们首次展示了与人类中和抗体 860-55D 的抗原结合片段 (Fab) 复合的 B19 病毒样颗粒 (VLP) 的低温电子显微镜 (cryo-EM) 结构。该模型被构建到 3.2 Å 分辨率的图谱中，并确定了 B19 衣壳表面的抗原性残基。抗体 860-55D 通过与由三个相邻 VP2 衣壳蛋白的残基形成的四级结构表位结合，连接 B19 的衣壳。细小病毒 B19 是一种常见的人类病原体，对儿童、孕妇以及镰状细胞病或艾滋病患者构成特殊威胁。目前，中和抗体是治疗急性 B19 感染最有效的方法。对 B19 抗原特性的研究将指导这些抗体的使用，并促进疫苗的开发。我们已经确定并报告了与人类中和抗体的 Fab 复合的 B19 病毒样颗粒 (VLP) 的高分辨率结构。该结构显示了由三个 VP2 蛋白形成的四级结构表位，并提供了有关宿主对人类 B19 病毒识别的详细信息。
