Novartis Institutes for BioMedical Research, Basel, Switzerland, Cambridge, MA, USA, and Emeryville, CA, USA.
Novartis Institutes for BioMedical Research, Basel, Switzerland, Cambridge, MA, USA, and Emeryville, CA, USA.
Immunity. 2019 Mar 19;50(3):668-676.e5. doi: 10.1016/j.immuni.2019.02.003. Epub 2019 Feb 26.
Human polyomaviruses cause a common childhood infection worldwide and typically elicit a neutralizing antibody and cellular immune response, while establishing a dormant infection in the kidney with minimal clinical manifestations. However, viral reactivation can cause severe pathology in immunocompromised individuals. We developed a high-throughput, functional antibody screen to examine the humoral response to BK polyomavirus. This approach enabled the isolation of antibodies from all peripheral B cell subsets and revealed the anti-BK virus antibody repertoire as clonally complex with respect to immunoglobulin sequences and isotypes (both IgM and IgG), including a high frequency of monoclonal antibodies that broadly neutralize BK virus subtypes and the related JC polyomavirus. Cryo-electron microscopy of a broadly neutralizing IgG single-chain variable fragment complexed with BK virus-like particles revealed the quaternary nature of a conserved viral epitope at the junction between capsid pentamers. These features unravel a potent modality for inhibiting polyomavirus infection in kidney transplant recipients and other immunocompromised patients.
人类多瘤病毒在全球范围内引起常见的儿童感染，通常会引发中和抗体和细胞免疫反应，同时在肾脏中建立潜伏感染，临床症状很少。然而，病毒的重新激活会导致免疫功能低下的个体发生严重的病理变化。我们开发了一种高通量的功能抗体筛选方法来研究针对 BK 多瘤病毒的体液免疫反应。这种方法能够从所有外周 B 细胞亚群中分离出抗体，并揭示出针对 BK 病毒的抗体库在免疫球蛋白序列和同种型（IgM 和 IgG）方面具有克隆复杂性，包括广泛中和 BK 病毒亚型和相关 JC 多瘤病毒的高频单克隆抗体。与 BK 病毒样颗粒复合的广泛中和 IgG 单链可变片段的冷冻电镜显示，在衣壳五聚体连接处存在一个保守病毒表位的四元结构。这些特征揭示了一种抑制肾移植受者和其他免疫功能低下患者中多瘤病毒感染的有效方式。
