Mapping Antigenic Epitopes on the Human Bocavirus Capsid
Mapping Antigenic Epitopes on the Human Bocavirus Capsid
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DOI：
10.1128/jvi.02998-15
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发表时间：
2016-05-01
影响因子：
5.4
通讯作者：
Agbandje-McKenna, Mavis
中科院分区：
文献类型：
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作者：
Kailasan, Shweta;Garrison, Jamie;Agbandje-McKenna, Mavis
人类博卡病毒（HBoV1 至 -4）是与幼儿肺炎和/或腹泻相关的新兴病原体。目前，尚无治疗方法或疫苗接种，因此需要研究这些病原体，以在分子和结构水平上了解其疾病机制，以制定控制策略。在这里，我们报告了六种 HBoV 单克隆抗体 (MAb) 片段复合物：HBoV1-15C6、HBoV2-15C6、HBoV4-15C6、HBoV1-4C2、HBoV1-9G12 和 HBoV1-12C1，通过冷冻电子显微镜和分辨率为 18.0 至 8.5 埃的三维图像重建确定。其中，15C6 MAb 与 HBoV1、HBoV2 和 HBoV4 发生交叉反应，而 4C2、12C1 和 9G12 MAb 仅识别 HBoV1。伪原子模型将 15C6 足迹分别映射到衣壳表面 DE 和 HI 环，分别位于 5 倍轴及其周围的凹陷处，这些是细小病毒科中的保守基序。 4C2、12C1 和 9G12 的封装跨越表面环路，这些表面环路组装了 2 倍/5 倍壁的部分（2 倍和 5 倍对称轴之间的凸起表面特征）和 3 倍突起的肩部。具有交叉反应性和毒株特异性的 MAb 足迹分别与 HBoV 衣壳表面上具有高和低序列/结构同一性的区域一致，并确定了开发这些病毒的肽疫苗的潜在区域。
Human bocaviruses (HBoV1 to -4) are emerging pathogens associated with pneumonia and/or diarrhea in young children. Currently, there is no treatment or vaccination, so there is a need to study these pathogens to understand their disease mechanisms on a molecular and structural level for the development of control strategies. Here, we report the structures of six HBoV monoclonal antibody (MAb) fragment complexes, HBoV1-15C6, HBoV2-15C6, HBoV4-15C6, HBoV1-4C2, HBoV1-9G12, and HBoV1-12C1, determined by cryo-electron microscopy and three-dimensional image reconstruction to 18.0-to 8.5-angstrom resolution. Of these, the 15C6 MAb cross-reacted with HBoV1, HBoV2, and HBoV4, while the 4C2, 12C1, and 9G12 MAbs recognized only HBoV1. Pseudoatomic modeling mapped the 15C6 footprint to the capsid surface DE and HI loops, at the 5-fold axis and the depression surrounding it, respectively, which are conserved motifs in Parvoviridae. The footprints for 4C2, 12C1, and 9G12 span the surface loops that assemble portions of the 2-/5-fold wall (a raised surface feature between the 2-fold and 5-fold axes of symmetry) and the shoulder of the 3-fold protrusions. The MAb footprints, cross reactive and strain specific, coincide with regions with high and low sequence/structural identities, respectively, on the capsid surfaces of the HBoVs and identify potential regions for the development of peptide vaccines for these viruses.