Department of Medical Microbiology, Laboratory of Clinical Virology, Academic Medical Center, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands.
Institute of Biotechnology & Department of Biosciences, University of Helsinki, Helsinki, 00014, Finland.
Sci Rep. 2017 Sep 21;7(1):12075. doi: 10.1038/s41598-017-12458-5.
Human parechovirus 3 (HPeV3), a member of the Picornavirus family, is frequently detected worldwide. However, the observed seropositivity rates for HPeV3 neutralizing antibodies (nAbs) vary from high in Japan to low in the Netherlands and Finland. To study if this can be explained by technical differences or antigenic diversity among HPeV3 strains included in the serological studies, we determined the neutralizing activity of Japanese and Dutch intravenous immunoglobulin batches (IVIG), a rabbit HPeV3 hyperimmune polyclonal serum, and a human HPeV3-specific monoclonal antibody (mAb) AT12-015, against the HPeV3 A308/99 prototype strain and clinical isolates from Japan, the Netherlands and Australia, collected between 1989 and 2015. The rabbit antiserum neutralized all HPeV3 isolates whereas the neutralization capacity of the IVIG batches varied, and the mAb exclusively neutralized the A308/99 strain. Mapping of the amino acid variation among a subset of the HPeV3 strains on an HPeV3 capsid structure revealed that the majority of the surface-exposed amino acid variation was located in the VP1. Furthermore, amino acid mutations in a mAb AT12-015-resistant HPeV3 A308/99 variant indicated the location for potential antigenic determinants. Virus aggregation and the observed antigenic diversity in HPeV3 can explain the varying levels of nAb seropositivity reported in previous studies.
人肠道病毒 3 型（HPeV3）是小 RNA 病毒科的一种病毒，在世界范围内频繁被检测到。然而，观察到的 HPeV3 中和抗体（nAbs）的血清阳性率在日本较高，而在荷兰和芬兰较低。为了研究这种差异是否可以用血清学研究中包含的 HPeV3 株的技术差异或抗原多样性来解释，我们测定了日本和荷兰静脉注射免疫球蛋白（IVIG）批次、兔 HPeV3 高免疫多克隆血清和人源 HPeV3 特异性单克隆抗体（mAb）AT12-015 对 HPeV3 A308/99 原型株和 1989 年至 2015 年间收集的来自日本、荷兰和澳大利亚的临床分离株的中和活性。兔抗血清中和了所有 HPeV3 分离株，而 IVIG 批次的中和能力不同，mAb 仅中和 A308/99 株。在 HPeV3 衣壳结构上对一组 HPeV3 株的氨基酸变异进行映射显示，大多数表面暴露的氨基酸变异位于 VP1 上。此外，在 mAb AT12-015 抗性 HPeV3 A308/99 变异株中氨基酸突变表明了潜在抗原决定簇的位置。病毒聚集和 HPeV3 中观察到的抗原多样性可以解释以前研究报告的 nAb 血清阳性率的差异。
